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President's Report on the Fourth Annual Meeting
of the Iowa Physiological Society, 1999

Presidents Report
Program
Abstracts

President's 1999 Annual Meeting Report

The fourth annual meeting of the Iowa Physiological Society (IPS, http://www.faseb.org/aps/chapters/iowa/iowa.htm) was held on April 23rd and 24th at Iowa State University (http://www.iastate.edu/) in Ames ( http://www.amesev.net/), Iowa. The IPS meets in conjunction with the larger Iowa Academy of Science (IAS, http://www.iren.net/ias). This joint meeting is beneficial to both organizations in that it brings together more physiologists than would be possible if the meetings were held separately. Perhaps this combination of state science academy meetings with state physiological society meetings can serve as a model for other states considering the formation of a physiological society. The Chair of the Physiology Section of the IAS also serves as President of the IPS and separate business meetings are held for both organizations at the annual meeting. This year we had a total of 20 papers presented in slide and poster formats (Program and Abstracts). Fourteen of the twenty eight posters displayed at the IAS Meeting were contributed by the members of the IPS. A nice spectrum of physiological topics were presented including sensory physiology, fish respiration, ion channels, shock and resuscitation techniques, vascular smooth muscle, hypertension, baroreceptor function and renal nerve physiology. Several viewing sessions of posters were possible both days and during the Saturday afternoon session each poster author was given a time slot to discuss their poster for the benefit the entire audience. This is an approach we have used twice and have found this technique very helpful in communicating the research findings as well as stimulating discussion. The traditional luncheon buffet on the second day of the meeting was hosted by the IPS and continues to be a popular event. It is held against the backdrop of the poster papers allowing informal discussion of the research. The luncheon was catered this year by a member of the IPS executive committee Richard McCabe.

A highlight of the meeting was made possible by a Lectureship Award from the American Physiological Society which helped sponsor Dr. Charles Tipton, Emeritus Professor of Physiology at the University of Arizona who gave a General Session Lecture before the entire Iowa Academy on Friday evening titled, The Iowa Wrestling Studies: From Athens To Iowa City. His presentation centered on his pioneering studies concerning the control of body mass, fluid balance and electrolyte balance in high school wrestlers during their training and certification for weight classification. Professor Tipton has been active in studies of microgravity sponsored by NASA and presented the APS Keynote Lecture after the Saturday afternoon luncheon buffet on the topic, Animal Models For Select Human Problems Created By A Microgravity Environment. Both of his presentations were very well received and we are grateful to the APS for their sponsoring assistance. We were pleased that Dr. Tipton attended the entire meeting and provided valuable discussion for most of the papers.

Following the Saturday morning slide presentation, the Iowa Physiological Society business meeting was held at which time committee reports were heard, the new IPS president elect was chosen and the election for the treasurer position was held. The new President of the Iowa Physiological Society is Luke H. Mortensen, Ph.D. (Physiology/Pharmacology, University of Osteopathic Medicine, Des Moines, IA 503112, (www.uomhs.edu/pharmacology/people/lm.htm). His e-mail address is lmortens@uomhs.edu . Piper Wall, Ph.D., DVM (Staff Scientist, Surgical Education Dept., Iowa Methodist Hospital in Des Moines, IA 50309) is the new President-elect of the IPS. Her e-mail address is pwall@dnx2.dux.com . Mark Chapleau, Ph.D. (Internal Medicine, University of Iowa, Iowa City, IA 52242, (www.vh.org/Welcome/UIHC/UIHCPhysDirectory/CardMDs/MarkChapleau.html) was elected to a three year term as Treasurer of the IPS. His e-mail is mark-chapleau@uiowa.edu. The fifth annual meeting of the IPS will take place April 21-22, 2000 at the Hotel Ft. Des Moines, Des Moines, IA.

Complete details of the fourth annual meeting of the IPS are available from our program and abstracts.

Russell Rulon, Past President, Iowa Physiological Society, rulonrus@luther.edu

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Program for the Meeting for the 1999 Meeting

Iowa Physiological Society Meeting with IAS Physiology Section
Memorial Union, Iowa State University, Ames, Iowa
Presiding: Russell Rulon, Chair & IPS President
Luke Mortensen, Vice Chair & IPS President elect

Friday, April 23, 1999

4:00-5:00 pm. Display of Physiology Posters at Iowa Academy of Science General Poster Session, Campanile Room.

8:00 pm. IAS General Sessions II Following the IAS Presidents' Banquet, Campanile & Cardinal Rooms
Charles M. Tipton, Professor Emeritus of Physiology at the University of Arizona, "The Iowa Wrestling Studies: From Athens to Iowa City".
 

Saturday, April 24, 1999

Iowa Physiological Society Meeting with IAS Physiology Section
Presiding: Russell Rulon, Chair & IPS President,
Luke Mortensen, Vice Chair & IPS President Elect

Rm. 150, Carver Bldg.

8:00 am. Informal viewing of physiology posters: All Physiology poster papers were first displayed in the General Poster Session of the IAS from 4:00-5:00 pm Friday. Posters were then be transferred to the Physiology Session for further viewing on Saturday from 8:30-9:00 am, 12:00-1:15 pm, and then from 2:00-4:00 pm each poster author(s) presented a brief introduction-discussion of their poster for the benefit of section members.

9:00 am. IAS PHYSIOLOGY SECTION BUSINESS MEETING. Piper L. Wall, Iowa Methodist Medical Center, Des Moines, IA was elected the 1999-2000 Physiology Section Co-Chair and will become the 2000-01 Chair.

9:15 am. 117. ACTH injections during gestation alter the piglet's HPA axis. M. F. HAUSSMANN, J.A. CARROLL, G. D. WEESNER and D. C. LAY, JR., 2356 Kildee Hall, Iowa State University, Ames, IA 50011.

9:30 am. 118. Physiological responses of walleyes to transportation and stocking procedures. J. A. FORSBERG1, R. C. SUMMERFELT1 and B. A. BARTON2, 1Iowa State University,Department of Animal Ecology, 124 Science II, Ames, IA 50011-3221; 2University of South Dakota, Department of Biology,414 East Clark Street, Vermillion, SD 57069-2390.

9:45 am. 119. Enalaprilat during resuscitation improves survival. P. WALL, M. FOLEY, F. RAYMOND, J. WITTKOPF, D. DAVIS, B. SOBCZAK, A. CHENDRASEKHAR, D. MOORMAN, G. TIMBERLAKE. Surgical Education Department, Iowa Methodist Medical Center, Des Moines, IA 50309.

10:00 am. 120. Effects of TEA and Maurotoxin on voltage-gated K+ channels expressed in Xenopus oocytes. B. C. NOLAN1, M. DE WAARD2 and T. HOSHI1, 1Department of Physiology & Biophysics and Neuroscience Graduate Program, University of Iowa, Iowa City, IA 52242. 2Institut Federatif Jean Roche Laboratoire de Neurobiolgie des Canaux Ioniques 13916 Marseille Cedex 20, France.

10:30 am. IOWA PHYSIOLOGICAL SOCIETY BUSINESS MEETING. Piper L. Wall, Iowa Methodist Medical Center, Des Moines, IA was elected the 1999-2000 IPS President Elect and will become the 2000-01 President.

12:00 n. IPS BUFFET LUNCH COMBINED WITH CONTINUED VIEWING OF PHYSIOLOGY P0STERS.

1:15 pm. APS KEYNOTE LECTURE: Animal models for select human problems created by a microgravity environment. CHARLES M. TIPTON, Professor Emeritus of Physiology & Surgery, University of Arizona, Tucson, Arizona 85721-0093.

Dr. Tipton is a world recognized authority on hypertension, influence of microgravity and physiological aspects of training for the sport of wrestling. He was at the University of Iowa for 21 years serving as Professor of Physical Education and Physiology as well as Professor of Bioengineering. At the University of Arizona, Dr. Tipton has held several positions including Head, Dept.of Exercise and Sport Sciences and Director or the School of Health Related Professions in addition to his appointment as Professor of Physiology and Surgery. He has been honored several times by the American College of Sports Medicine. He is Chair of the APS Section on Environmental and Exercise Physiology, a member of several NASA Committees and member of the editorial board of the Journal of Applied Physiology. We are grateful to the American Physiological Society for their support of Dr. Tipton's visit.

2:00. 121. Models and mind-sets for teaching neurophysiology. C. DREWES, Department of Zoology, Iowa State University, Ames, IA 50011.

2:15 pm. 116. The Role of Particles in the Perception of Flavors. LEI LIU and E. G. HAMMOND, Food Science and Nutrition, Iowa State University, Ames, IA 50011.

2:30-4:00 pm. POSTER DISCUSSION SESSION (Each presenter gave a short oral summary of their poster and then answered questions from the floor.)

Poster. 122. Inability to increase temperature as a marker for decreased survival. P. WALL, F. RAYMOND, D. DAVIS, B. SOBCZAK, A. SIDNEY, T. OHLEY, J. WITTKOPF, S. SIDNEY, D. NANDAL, G. TIMBERLAKE and D. MOORMAN. Surgical Education Dept., Iowa Methodist Medical Center, Des Moines, IA 50309.

Poster. 123. Effects of continuous furosemide in oleic acid lung injury. C. REISING, P. WALL, A. CHENDRASEKHAR, J. BRATZ, C. MUNSTERMAN, F.RAYMOND, D. MOORMAN and G. TIMBERLAKE. Surgical Education Dept., Iowa Methodist Medical Center, Des Moines, IA 50309.

Poster. 124. Influence of continued crystalloid resuscitation on outcome. P. WALL, F. RAYMOND, D. DAVIS, B. SOBCZAK, A. SIDNEY, T. OHLEY, J. WITTKOPF, A. CHENDRASEKHAR, D. MOORMAN, G. TIMBERLAKE. Surgical Education Dept., Iowa Methodist Medical Center, Des Moines, IA 50309.

Poster. 125. Hypertonic saline dextran followed by LRS/dextran mix: improved 48hr survival vs lactated Ringer's. P. WALL, F. RAYMOND, D. DAVIS, B. SOBCZAK, A. SIDNEY, T. OHLEY, J. WITTKOPF, A. TESAR, A. CHENDRASEKHAR, G. TIMBERLAKE. Surgical Education Dept., Iowa Methodist Medical Center, Des Moines, IA 50309.

Poster. 126. Gatorade(tm) pre-hemorrhage associated with decreased mortality. P. WALL, F. RAYMOND, D. DAVIS, B. SOBCZAK, A. SIDNEY, T. OHLEY, J. WITTKOPF, A. CHENDRASEKHAR, D. MOORMAN, G. TIMBERLAKE. Surgical Education Dept., Iowa Methodist Medical Center, Des Moines, IA 50309.

Poster. 127. An electron microscopy study of the renal nerves in C57 black mice. V.P.S. FAZAN, S. Y. MA, F. M. ABBOUD, and M. W. CHAPLEAU. University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242.

Poster. 128. Angiotensin-induced activation of "silent" renal sympathetic nerves in mice. X. Y. MA, F. M. ABBOUD and M. W. CHAPLEAU. University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242.

Poster. 129. Genistein decreases force development in aortic rings of borderline hypertensive rats by selective inhibition of calcium mobilization. J. AERTS, D. B. STRATTON and R. J. MORROW. Drake University, Hypertension Research Center, Departments of Biology and Pharmaceutical Sciences, Des Moines, IA 50311.

Poster. 130. Comparison of contractile responses of isolated bovine tail artery and vein to norepinephrine, a,ß-meATP and field stimulation. M. IOUDINA and D. C. DYER, Dept. of Biomedical Sciences, Iowa State
University, Ames, IA 50011.

Poster. 131. Perinatal treatment with genistein provides protection from hypertension in male but not female spontaneously hypertensive rats. D. B. STRATTON and R. J. MORROW. Drake University, Hypertension Research Center, Department of Biology and Pharmaceutical Sciences, Des Moines, IA 50311.

Poster. 132. Mechanism of impaired baroreflex control of sympathetic nerve activity in hypertensive renin-angiotensinogen double transgenic mice. X. Y. MA, R. A. SHAFFER, C. D. SIGMUND, F. M. ABBOUD and M. W. CHAPLEAU. University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242.

Poster. 133. Parasympathetic and sympathetic contributions to heart rate and arterial pressure variability in conscious mice. R. FAZAN JR., R. A. SCHAFFER, F. M. ABBOUD and M. W. CHAPLEAU. University of Iowa
and Veterans Affairs Medical Center, Iowa City, IA 52242.

Poster. 134. Carotid baroreflex control of arterial pressure studied by sequential carotid occlusion in mice. S. S. MEYRELLES and M. W, CHAPLEAU, University of Iowa and Veterans Affairs Medical Ctr., Iowa City, IA 52242.

Poster. 135. L-NAME-induced hypertension in female borderline hypertensive rats is reversed by estrogen. J-M CENTER-HOWDEN, D. B. STRATTON and R. J. MORROW. Drake University, Hypertension Center, Departments of Biology and Pharmaceutical Sciences, Des Moines, IA 50311.

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ABSTRACTS

Abstracts of Oral and Poster Presentations
Selected for Presentation at the 1999 Meeting

116. THE ROLE OF PARTICLES IN THE PERCEPTION OF FLAVORS. L Liu and EG Hammond, Food Science and Human Nutrition, Iowa State University, 2312 Food Science Building, Iowa State University, Ames, IA 50011. The flavor thresholds of 2-pentanone, 2-heptanone, and 2-nonanone were determined when observers held their mouthparts still and when they were allowed to move their lips and tongues. The threshold with the mouthparts still was significantly higher than that with the mouthpart moving. Flavor descriptors applied to mixtures of amino acids, salts and flavor potentiators, which were designed to simulate crab flavor, also shifted substantially when tasted with still versus moving mouth parts. The differences observed with still and moving mouth parts were attributed to particles, which are generated when the lips are parted or the tongue is pulled away from the oral palate.

117. ACTH INJECTIONS DURING GESTATION ALTER THE PIGLET'S HPA AXIS. MF Haussmann, JA Carroll, GD Weesner and .DC Lay, Jr., 2356 Kildee Hall, Iowa State University, Ames IA 50011. Modem livestock production is potentially stressful due to confinement and crowding. When a pregnant sow is stressed, cortisol is released into the circulation and will cross the placenta to possibly effect the fetal hypothalamus. This study was designed to examine the physiology of piglets whose dams were injected with ACTH during gestation. Sixteen pregnant sows, were assigned to either the control group (C, n=8) or the ACTH injected group (A, n=8). The C sows were given no treatment while the A sows were administered an i.v. injection of ACTH (1 IU/kg of body weight) at 6, 7, 8, 9, 10, 11 and 12 weeks of gestation. At birth, 1 month and 2 months of age piglets were weighed and one male of average weight was sacrificed. The hypothalamus, pituitary glands and adrenal glands were immediately obtained, weighed, and stored in liquid nitrogen. Hypothalamic CRH and $ -Endorphin, as well as mRNA for the adrenal ACTH receptor were quantified. At 2.5 months of age one pig from each litter was mixed with unfamiliar pigs and blood was obtained to determine plasma cortisol concentrations. Results indicate that A pigs tended to have larger pituitary glands than C pigs at 2 months of age. The A pigs had greater mRNA for the ACTH -receptor and concentrations of CRH than C pigs, but they had a lower concentration of b -Endorphin. In response to mixing, A pigs had higher concentrations of plasma cortisol than C pigs. These results indicate that ACTH injections to sows during gestation alter the HPA axis of their offspring.

118. PHYSIOLOGICAL RESPONSES OF WALLEYES TO TRANSPORTATION AND STOCKING PROCEDURES. JA Forsberg1, RC Summerfelt1, and BA Barton2, 1Iowa State University, Department of Animal Ecology, 124 Science 11, Ames, IA 50011-3221, 2 University of South Dakota, Department of Biology, 414 East Clark Street, Vermillion, SD 57069-2390. There is a concern that walleye fingerlings transported by truck from Rathbun Fish Hatchery, Moravia, Iowa, to Lake East Okoboji, Spirit Lake, Iowa may be experiencing stress that reduces post-stocking survival in Lake East Okoboji. To measure the physiological responses of walleyes to transportation and stocking procedures, we collected blood samples from walleye during two transportation events. We also measured water quality variables in hauling tanks, raceways at Rathbun and Spirit Lake fish hatcheries, and in Lake East Okoboji. To reduce hauling stress, sodium chloride (0.5%) was added to four of the eight hauling tanks prior to placing the fish into the tanks. Sodium chloride (0.4%) and sodium bicarbonate (0.1%) were dissolved into the remaining four hauling tanks. Whole blood concentrations of sodium were similar in samples taken before and during the haul, but decreased significantly 2h after stocking. Sodium gradually returned to preload levels during the 72h following stocking. Blood pH values prior to the haul and 72h posthaul were similar; pH increased significantly 2h after stocking into the lake. The addition of sodium bicarbonate to hauling tanks increased water pH by 0.7 pH units and alkalinity by 314 mg/L, but did not significantly affect blood chemistry.

119. ENALAPRILAT DURING RESUSCITATION IMPROVES SURVIVAL. P Wall, M Foley, F Raymond, J Wittkopf, D Davis, Bsobczak, A Chendrasekhar, D Moorman, and G Timberlake, Surg Ed Dept, Iowa Methodist Medical Center, Des Moines, IA 50309. Enalaprilat may be useful in trauma resuscitation. Methods: Male Wistar-Furth rats were anesthetized, instrumented, and hemorrhaged (H) (MAP=35-40 mmHg) till MAP =/< 30mmHg for 10min or <25mmHg for 1min or 120min elapsed. Resuscitation (R) with lactated Ringer's (LRS) continued for 3hr (MAP=75-80mmHg). 9 received only LRS (C). 7 received enalaprilat (0.06mg/kg) 5 & 30min into R (Early). 7 received enalaprilat 30 & 60min into R (Late). Results: Start R base excess: C=-12.5 +/- 1.1, Early=-13.2 +/- 0.8, Late=-l0.4 +/- 0.7. LRS given (ml/kg): C=72 +/- 18, Early=125 +/- 24 (p<0.05 vs. others), Late=64 +/- 15. #p=0.008 Early vs LRS. *p=0.05 Early vs LRS & Late vs LRS.. Conclusions: Enalaprilat early during resuscitation improved survival. Delaying enalaprilat administration improved survival but without an increase in fluid requirements. (Support: IMMC, SpaceLabs. ISU, Bayer.)

120. EFFECTS OF TEA AND MAUROTOXIN ON VOLTAGE-GATED K* CHANNELS EXPRESSED IN XENOPUS OOCYTES. BC Nolan1, M De Waard2 and T Hoshi1, 1Department of Physiology & Biophysics and Neuroscience Graduate Program, University of Iowa, Iowa City, IA 52242. 2Institut F6d6ratif Jean Roche Laboratoire de Neurobiologie des Canaux Ioniques13916, Marseille Cedex 20, France. Maurotoxin (MTX) is a small peptide toxin (34 residues) isolated from scorpionid Scorpio maurus palmatu and it is known to block certain voltage-gated K+ channels (Kharrat et al., Eur J Biochem 242, 491, 1996). To investigate the biophysical and molecular mechanisms of the toxin action, we expressed Shaker potassium channels with disrupted N-type inactivation (D 6-46) and with little C-type inactivation in Xenopus oocytes by RNA injection. The Shaker K+ currents in the presence of different concentrations of the toxin were measured using the conventional two-electrode voltage-clamp method. As shown previously, we found that extracellular tetraethylammonium (TEA) was more effective in blocking the ShBD 6-46:T449Y channel than the ShBD 6-46:T449V channel. In contrast, MTX was much more effective in reducing the ShBD 6-46:T449V activity. The ShBD 6-46:T449Y channel was virtually unaffected by MTX (up to 100 nM). The results suggest that the residue 449 located in the outer mouth of the K+ channel pore may in part mediate the MTX action and that its underlying mechanism is different from that for the external TEA action.

121. MODELS AND MIND-SETS FOR TEACHING NEUROPHYSIOLOGY. C. Drewes, Department of Zoology, Iowa State University, Ames, IA 60011. I will present some innovative instructional materials and activities related to the teaching of nervous system function and structure. The materials are appropriate for courses in general biology or physiology, at either high school or college levels. I will show how to make and use tangible models that illustrate important features and functions of Integral membrane proteins in nerve cells. The models are made from inexpensive materials and have moving parts. They especially illustrate dynamics of gating (i.e., channel opening and closing) in voltage-gated sodium channels and voltage-gated potassium channels, as well as ligand-gated channels. Hands-on manipulation of these models strongly reinforces key concepts of neurophysiology, such as the action potential, while promoting active learning and Inquiry by students. The presentation also addresses certain misconceptions and distortions related to nerve cell structure and function that are commonly perpetuated in textbooks and other educational materials. Take-home models and an illustrated instructional booklet will be provided.

122. INABILITY TO INCREASE TEMPERATURE AS A MARKER FOR DECREASED SURVIVAL. P Wall, F Raymond, D Davis, B Sobczak, A Sidney, T Ohley, J Wittkopf, S Sidney, D Nandal, G Timberlake, and D Moorman, Surg Ed Dept, Iowa Methodist Medical Center, Des Moines, IA 50309. The ability of mitochondria to restore ATP is critical to shock reversibility. Since metabolic processes generate heat, we investigated the rate of temperature change during resuscitation (R) from hemorrhagic shock (H). Methods: 25 male Wistar-Furth rats were anesthetized, instrumented, and hemorrhaged (MAP=35-40mmHg) till MAP +/- 30mml-lg for 10min or <25mmHg for 1min or 120min elapsed. Room temperature lactated Ringer's (LRS) was delivered for 3hr as needed (MAP=75-80mmHg). Results: 3 died in H & 3 died in R. Blood loss, start of resuscitation hematocrit and base excess, and LRS given did not predict survival. (p<.05 between groups after 255 minutes, ANOVA). Conclusions: Longer survival after hemorrhagic shock is associated with a more rapid rise in body temperature during early resuscitation. The exact mechanism for this association is under further investigation. (Support: IA Meth Med Ctr, SpaceLabs Medical, Diametrics, ISU, Bayer).

123. EFFECTS OF CONTINUOUS FUROSEMIDE IN OLEIC ACID LUNG INJURY. C Reising, P Wall, A Chendrasekhar, J Bratz, C Munsterman, F Raymond, D Moorman, and G Timberlake, Surg Ed Dept, Iowa Methodist Medical Center, Des Moines, IA 50309. Furosemide improves ventilation perfusion matching in acute lung injury. Methods: 11 mongrel dogs were anesthetized, instrumented, ventilated (volume control CMV), and given oleic acid (0.1 ml/kg) iv. Pulmonary artery occlusion pressure (PAOP) and stroke volume index (SVI) were maintained in all dogs with lactated Ringer's. 2hr after oleic acid, 6 dogs started continuous furosemide (0.2mg/kg/hr). Results: No PAOP, SVI, cardiac index, or arterial PCO2 differences existed between groups at any time. Volume infused didn't differ but urine output was greater in furosemide dogs (4.7 +/- 1.5L vs 1.6 +/- 0.5L, p<0.01). PaO2/FiO2 ratio improved with furosemide (PaO2/FiO2 130 +/- 55 to 249 +/- 75 vs 115 +/- 41 to 105 +/- 20, p=0.05). Shunt fraction decreased with furosemide (D Qs/Qt -0.17 +/- 0.06 vs -0.01 +/- 0.05, p<0.05). PEEP requirements trended toward reduction with furosemide (9.5 +/- 4.2 vs 14.3 +/- 2.5cm H2O, p=0.10). Gastric (G) or intestinal (1) intraluminal PCO2 differed by 4hr after oleic acid.Conclusions: Continuous low dose furosemide improved pulmonary indices and GI mucosal energy status in this canine model of acute lung injury. (Support: IMMC, SpaceLabs, VA Med Ctr.)

124. INFLUENCE OF CONTINUED CRYSTALLOID RESUSCITATION ON OUTCOME. P Wall, F Raymond, D Davis, B Sobczak, A Sidney, T Ohley, J Wittkopf, A Chendrasekhar, D Moorman, and G Timberlake, Surg Ed Dept, Iowa Methodist Medical Center, Des Moines, IA 50309. Previously our hemorrhagic shock model only involved 3hr of resuscitation (R). Methods: 14 male Wistar-Furth rats were anesthetized, instrumented, and hemorrhaged (MAP=35-40mmHg) till MAP +/- 30mmHg for 10min or <25mmHg for 1min or 120min elapsed. R with lactated Ringer's (LRS, I ml/min) as needed (MAP=75-80mmHg) occurred for 3hr or 24hr. Results: 3hr R rats lost 35 +/- 3ml/kg of blood, started R with a base excess (BE) of -16.5V 1.6, and received 98 +/- 25ml/kg LRS. 24hr R rats lost 27 +/- 3ml/kg of blood, started R with a BE of -12.9 +/- 1.4, and received 471 +/- 119ml/kg LRS. Conclusions: Continued R with LRS failed to improve survival after severe hemorrhagic shock in this model. Continuing -cardiovascular support with LRS without other Interventions is insufficient to improve outcome in this model. (Support: IMMC, VA Med Ctr, ISU, Bayer.)

125. HYPERTONIC SALINE DEXTRAN FOLLOWED BY LRS/DEXTRAN MIX: IMPROVED 48HR SURVIVAL VS LACTATED RINGER'S. P Wall, F Raymond, D Davis, B Sobczak, A Sidney, T Ohley, J Wittkopf, A Tesar, A Chendrasekhar, and G Timberlake, Surg Ed Dept, Iowa Methodist Medical Center, Des Moines, IA 50309. Resuscitation (R) with hypertonic saline dextran (HSD) holds some theoretical benefits over lactated Ringer's (LRS). Methods: 22 male Wistar-Furth rats were anesthetized, instrumented, and, 30min later, hemorrhaged (MAP=35-40mmHg) till MAP +/- 30mmHg for 10min or <25 mmHg for 1min or 120min elapsed. R consisted of intravenous fluid for 3hr (MAP>75mmHg). 6 rats received 4ml/kg of 7.8% NaCl in 6% dextran 70 at 0.25 ml/min followed by a 6% dextran 70/lactated Ringer's mixture at 1 ml/min as needed. 16 rats received LRS at 1 ml/min as needed. All rats were followed 24hr before euthanasia. Results: HSD rats received 4 +/- 0ml/kg HSD and 8.4 +/- 2.3ml/kg dextran 70/LRS mix. LRS rats received 87.7 +/- 14.7ml/kg LRS. ap<0.05, bp<0.1 vs LRS, c 2.

R Fluid

 Mortality in 3hr R Mortality <24hr Blood loss ml/kg Start R BE 2 hr R BE 2hr R PCV
HSD 0 of 6a 0 of 6b 26.8 +/- 5.1 -12.0 +/- 0.7 -6.5 +/- 0.9 26 +/- 1
LRS 3 cf 16 10 of 16 29.2 +/- 2.5 -15.1 +/- 1.1 -7.1 +/- 1.0 28 +/- 2

Conclusions: Theoretical benefits of HSD resuscitation have been noted in short term models. This study shows resuscitation with HSD followed by a dextran 70/LRS mix conferred a significant 24hr survival advantage versus LRS. (Support: IMMC, SpaceLabs, Diametrics, ISU, Bayer.)

126. GATORADE (TM) PRE-HEMORRHAGE ASSOCIATED WITH DECREASED MORTALITY. P Wall, F Raymond, D Davis, B Sobczak, A Sidney, T Ohley, J Wittkopf, A Chendrasekhar, D Moorman, and G Timberlake, Surg Ed Dept, Iowa Methodist Medical Center, Des Moines, IA 50309. Overnight fasting is common in hemorrhage models and in elective surgery. Methods: 18hr pre-hemorrhage, male Wistar-Furth rats were allowed: (1) food and water (FW), (2) Gatorade (TM); (G), or (3) water (W). Rats were anesthetized (ketamine/pentobarbital), instrumented, and, 30min later, hemorrhaged (H) (MAP=35-40mmHg) until MAP =/< 30mmHg for 10min or <25mmHg for 1min or 120min elapsed. Resuscitation (R) with lactated Ringer's (1ml/min) continued for 3hr (MAP=75-80mmHg) after which rats were followed 24 to 48hr before euthanasia. Results: Of the 17 FW rats, 1 died during H and 3 died during R for 24% early mortality. Of the 5 G rats, 0 died during H or R for 0% early mortality. These 5 rats drank from 15 to 100 ml of Gatorade (TM). Of the 10 W rats, 2 died during H and 2 died during R for 40% early mortality (p=0.05 vs fed rats, c 2). Start H base excess, blood loss, and start R base excess, hematocrit, total plasma protein, and temperature were similar in each group. Conclusions: Fasting is an important experimental variable that must be considered when comparing outcomes obtained in hemorrhagic shock models. The provision of a glucose/electrolyte solution overnight was associated with a lower mortality than occurred in the fasted rats in these small groups. Whether this effect is significant will be investigated with more rats in each group. (Support:IMMC, SpaceLabs, ISU, Bayer.)

127. AN ELECTRON MICROSCOPY STUDY OF THE RENAL NERVES IN C57 BLACK MICE. VPS Fazan, XY Ma, FM Abboud, and MW Chapleau, University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242. The aim of this study was to describe the general morphological aspects and to obtain morphometric parameters for the extrinsic renal nerve in C57BL/6 mice. The major renal nerve innervating the left kidney was isolated in 3 mice. Thin sections of the nerve segments were then examined by the transmission electron microscope. The renal nerve averaged 34.3 +/- 2.4 m rn in diameter and 755 +/- 114 m m2 in area. The renal nerve contained an average of 709 +/- 86 unmyelinated fibers and only 3.6 +/- 1.3 myelinated fibers. The axon diameter of myelinated and unmyelinated fibers averaged 2.7 +/- 0.6 m m and 0.75 +/- 0.03 m m respectively. The diameter of the unmyelinated fibers ranged from 0.3 to 2.0 m m and the distribution histogram was unimodal. The majority of fibers (85%) had diameters between 0.6 and 1.0 m m. These results are similar to those obtained for renal nerves of rats with respect to the predominance of unmyelinated fibers. However, the diameter of unmyelinated fibers is larger in rats and the distribution histogram of rat unmyelinated fibers is bimodal in contrast to the unimodal distribution in mice. The morphologic description of the renal nerves in mice provides baseline data for further investigations of the structural basis of altered autonomic reflexes. The results will be useful in analysis of genes influencing development and structure of sympathetic and sensory innervation of the kidney in genetically manipulated mice. Fulbright, CAPES, NIH HL14388.

128. ANGIOTENSIN-INDUCED ACTIVATION OF "SILENT" RENAL SYMPATHETIC NERVES IN MICE. XY Ma, FM Abboud and MW Chapleau, University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242. Angiotensin (AII) promotes hypertension in part through its direct vasoconstrictor action and by attenuation of reflex inhibition of sympathetic nerve activity (SNA). The goal of this study was to determine effects of AII on renal SNA in mice. Arterial blood pressure (BP) and efferent renal SNA were recorded in anesthetized mice during i.v. bolus injections of AII (4-16 ng/,g) and norepinephrine (NE, 0.1-0.5 m g/g) or phenylephrine (PE, 1-5 m g/g). Baseline BP averaged 77 +/- 1(SE) mmHg (n=5). NE and PE increased BP (+55 +/- 4 mmHg) and essentially abolished phasic SNA (-92 +/- 9%, n=4). In contrast, an equal pressor dose of AII (+53 +/- 3 mmHg, n=5) caused a biphasic response; inhibition of phasic SNA followed by activation of continuous SNA that exceeded baseline activity (+229 +/- 109%, P<.05). The AII-induced activation of continuously discharging SNA was dose-dependent and was prevented by the AII receptor blocker saralasin (0.1 m g/g; iv, n=4). The ganglionic blocker hexamethonium (30 m g/g) abolished resting phasic SNA but did not reduce AII-induced continuous SNA (n=4). In baroreceptor denervated and vagotornized mice, AII failed to inhibit phasic SNA but continued to trigger continuous SNA. We conclude that AII acutely activates previously silent renal sympathetic nerves that discharge in a continuous pattern distinctly different than the normal resting phasic SNA. AII-activated SNA may exert unique actions on renal function.

129. GENISTEIN DECREASES FORCE DEVELOPMENT IN AORTIC RINGS OF BORDERILINE HYPERTENSIVE RATS BY SELECTIVE INHIBITION OF CALCIUM MOBILIZATION. J Aerts, DB Stratton and RJ Morrow, Drake University, Hypertension Research Center, Departments of Biology and Pharmaceutical Sciences, Des Moines, IA 50311. In response to stress, borderline hypertensive rats (BHR) develop persistent hypertension, part of which can be attributed to vascular changes. This study was designed to evaluate possible vascular effects of genistein (GEN), a phytoestrogen and tyrosine kinase inhibitor, on isometric force development in aortic rings from unstressed BHRs. Specifically, do adrenergically stimulated arterial rings exposed to GEN develop less force and, if so, is altered calcium mobilization a factor? To determine this, rings were pretreated with 8.5x10-5 M GEN and subsequently contracted with 1 micromolar phenylephrine (PE) in either physiologic saline (PS), calcium-free PS, or PS plus nifedipine. By selective comparisons of the force developed under these conditions, estimates were made for the calcium contribution of the sarcoplasmic reticulum (SR), voltage-operated channels (VOCCs), and receptor-operated channels (ROCCs). GEN pretreated rings produced significantly less isometric force in response to PE than untreated controls. This decrease in force appears to be primarily due to decreased mobilization of calcium from the SR and through ROCCs. The contribution of force through VOCCs appeared to be unaltered. Thus, the reported anti hypertensive effects of GEN might result, in part, from decreased alpha agonist-induced calcium mobilization in blood vessels.

130. COMPARISON OF CONTRACTILE MSPONSES OF ISOLATED BOVINE TAIL ARTERY AND VEIN TO NOREPINEPHRINE, (X,P-MEATP AND FIELD STIMULATION. M. Ioudina and DC Dyer, Dept. Biomedical Sciences, Iowa State University, Ames, IA, 50011. It has been shown by Hill and Dyer (1997) that norepinephrine (NE) causes contraction of the isolated tail artery primarily through activation of a l-adrenoceptors. We found that NE developed a significantly higher contractile force in the isolated artery than In the vein. However, EC50 for NE in vein was smaller than in artery. a ,b -MeATP, stable ATP analogue, caused contraction in both vessels, but was more potent in the artery than in vein. Suramin, purinergic receptor antagonist, caused inhibition of contractile responses to a ,b -MeATP in both vessels, whereas PPADS, another purinergic antagonist, caused much less inhibition. Electrical field stimulation with constant current 150 mA, 1 msec duration, at 1-32 Hz frequency range, caused frequency dependent contraction in the artery due to neurotransmitter(s) release. However, these same electrical settings caused contraction in only one of seven vein preparations and in this one preparation the contraction was small. Summary: The increased sensitivity of the vein vs. artery to NE may be due to: activation of different adrenoceptors (a 1 + a 2 vs. a 1); lack of innervation and/or a greater number of adrenoceptors. These possibilities are currently being investigated. There is evidence of purinergic (P2X) receptors on both vessels. It appears that mechanism(s) of vascular tone regulation in vein and artery may differ. Supported in part by USDA formula funds.

131. PERINATAL TREATMENT WITH- GENISTEIN PROVIDES PROTECTION FROM HYPERTENSION IN MALE BUT NOT FEMALE SPONTANEOUSLY HYPERTENSIVE RATS. DB Stratton and RJ Morrow, Drake University, Hypertension Research Center, Departments of Biology and Pharmaceutical Sciences, Des Moines, IA 50311. The authors have previously shown that genistein (GEN) delays hypertension development in male and ovariectomized female spontaneously hypertensive rats (SHR). The purpose of this study was to determine if the administration of GEN during the perinatal period (gestation and weaning) could provide protection from hypertension to the pups. To evaluate this, SHR were bred and immediately started on daily subcutaneous injections of either GEN (1 mg/kg) or vehicle (VEH) which continued through weaning of the pups. Following weaning, the females were ovariectomized (OVX) and the males were left untreated. At twelve weeks of age, all animals were fitted with femoral arterial catheters and a full blood pressure profile was recorded. VEH-treated mothers produced offspring with hypertensive levels of systolic, diastolic and mean blood pressure in both males and OVX females. GEN-treated mothers produced male offspring with significantly reduced blood pressures but no reduction in blood pressure was observed in OVX females. The results of these studies suggest that perinatal exposure to genistein affords some protection from the otherwise inevitable development of hypertension in male but not ovariectornized female SHR.

132. MECHANISMS OF IMPAIRED BAROREFLEX CONTROL OF SYMPATHETIC NERVE ACTIVITY IN HYPERTENSIVE RENIN-ANGLOTENSINOGEN DOUBLE TRANSGENIC MICE. XY Ma, RA Shaffer, CD Sigmund, FM Abboud and MW Chapleau, University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242. In chronic hypertension, the baroreflex (BR) function curve is reset to higher blood pressure (BP) (increased midpoint) and the slope of the curve (gain) may be decreased. The goal of this study was to determine mechanisms responsible for increased midpoint and decreased BR gain in chronic hypertension. Double transgenic mice carrying human renin and angiotensinogen genes (R+/A+) and littermate controls were studied. BP measured intraarterially was significantly elevated in conscious R+/A+ mice (n=5) compared with control mice (n=9) (131 +/- 6 vs. 101 +/- 5 mmHg, p<0.05). The mice were anesthetized and renal sympathetic nerve activity (SNA) was measured during nitroprusside and phenylephrine (iv) induced changes in BP. The SNA-BP data were fit to a sigmoidal function. Anesthesia normalized BP in R+/A+ mice (69 +/- 4 and 74 +/- 4 mmHg in control and R+/A+). Consequently, the midpoint of the BR curve was not significantly different in control (n=6) vs. R+/A+ mice (n=6). In contrast, BR gain was significantly decreased in anesthetized R+/A+ mice (1.8 +/- 0.5 %/mmHg, n=6, p<0.05) compared with control mice (3.1 +/- 0.7 %/mmHg, n=6). Blockade of angiotensin AT-1 receptors acutely restored BR gain in R+/A+ mice (3.0 +/- 0.9%/mmHg, n=6). We conclude that 1) BR gain is significantly decreased in R+/A+ mice despite normalization of both BP and midpoint of BR curve by anesthesia; and 2) BR gain can be rapidly restored by blocking angiotensin receptors suggesting that the decreased gain is not caused by chronic structural vascular changes.

133. PARASYMPATHETIC AND SYMPATHETIC CONTRIBUTIONS TO HEART RATE AND ARTERIAL PRESSURE VARIABILITY IN CONSCIOUS MICE. R Fazan Jr., RA Shaffer, FM Abboud and MW Chapleau, University of Iowa and Veterans Affairs Medical Ctr., Iowa City, IA 52242. Physiological studies are required to understand phenotypic expression in genetically manipulated mice. Little is known regarding heart rate (HR) and blood pressure (BP) variability in mice. Reports have suggested a dominant role of the sympathetic nervous system (SNS) with minimal influence of the parasympathetic system (PNS). The goal of this study was to determine SNS and PNS contributions to HR and BP variability in conscious unrestrained mice. One day after implanting a carotid catheter, BP of C57BL/6 mice was recorded. BP and HR averaged 124 +/- 6 / 86 +/- 4 mmHg and 489 +/- 14 bpm. Mean values, standard deviations (SD) and power spectra (FFT) were calculated for HR and diastolic BP. Spectra were integrated into low (LF:0.l-lHz) and high (HF:l-5Hz) frequency bands. The b -receptor blocker propranolol (n=5) decreased HR (-91 +/- 6 bpm) and reduced HR-SD from 31 +/- 3 to 17 +/- 2 bpm. The muscarinic antagonist atropine (n=6) increased HR (+98 +/- 9 bpm) and reduced HR-SD to 13 +/- 2 bpm. The changes in HR were accompanied by parallel changes in BP. Propranolol decreased LF-HR variability by 56 +/- 7% as well as LF-BP variability but did not influence either HR or BP variability at HF. Atropine decreased LF and HF-HR variability by 65 +/- 3 and 32 +/- 3% respectively, and also decreased BP variability at LF and HF. We conclude that both SNS and PNS tonically modulate HR and contribute to LF-HR and BP variability in conscious mice. However, HF-HR and BP variability is modulated primarily by the PNS.

134. CAROTID BAROREFLEX CONTROL OF ARTERIAL PRESSURE STUDIED BY SEQUENTIAL CAROTID OCCLUSION IN MICE. SS Meyrelles and MW Chapleau, University of Iowa and Veterans Affair's Medical Ctr., Iowa City, IA 52242. The ability to genetically manipulate mice provides an opportunity to investigate molecular mechanisms determining baroreflex (BR) sensitivity. The goals of this study were to develop a method to selectively evaluate carotid sinus BR control of blood pressure (BP) in mice and to demonstrate modulation of the reflex by local generation of oxygen radicals in carotid sinus adventitia. BP and carotid sinus pressures (CSP) were measured in anesthetized mice. Baseline BP averaged 79 +/- 6 mmHg (n=7). Changes in BP were measured in response to unilateral occlusion of one carotid artery (UCO) for 20s followed by additional occlusion of the contralateral carotid artery (BCO) for 20s. BIP did not change during UCO (+5 +/- 2 mmHg) but increased significantly during BCO (+18 +/- 2 mmHg, n=7). Reversing the sequence of occlusions did not influence the results. The reflex increase in BP was abolished after carotid sinus denervation (n=2). Oxygen radicals were acutely generated by topical application of xanthine (X, 0.1mM) and xanthine oxidase (XO, 60 mU/ml to carotid sinuses (n=7). In the presence of X+XO, the BP response to BCO decreased from +18 +/- 2 to +6 +/- 2 mmHg. BCO decreased CSP to the same extent before and during X+XO (-51 +/- 8 and -49 +/- 8 mmHg). The reflex was restored upon washout of X+XO (+18 +/- 4 mmHg). In conclusion, sequential carotid occlusion provides a method to selectively investigate the carotid BR in mice. The results demonstrate that generation of oxygen radicals in carotid sinus decrease BR sensitivity.

135. L-NAME-INDUCED HYPERTENSION IN FEMALE BORDERLINE HYPERTENSIVE RATS IS REVERSED BY ESTROGEN. J-M Center-Howden, DB Stratton and RJ Morrow, Drake University, Hypertension Research Center, Departments of Biology and Pharmaceutical Sciences, Des Moines, IA 50311. We have previously shown that L-NAME promotes significant hypertension in male borderline hypertensive rats (BHR) which is sustained after L-NAME withdrawal. The purpose of this study was to determine if L-NAME induces persistent hypertension in female BHR and, if so, is it estrogen-sensitive. At four weeks of age BHR were either ovariectornized (OVX) or were subjected to sham surgery which left ovaries intact (OVI). Starting at eight weeks of age they were treated for five weeks either with L-NAME in their drinking water (75 mg/liter) or with ordinary tap water. Systolic blood pressure, body weight, water and L-NAME consumption were measured and recorded weekly. At thirteen weeks of age, L-NAME was withdrawn and OVX animals were given daily intraperitoneal injections of either estradiol (E2) (0.1 mg/kg) or vehicle (VEH) for four additional weeks. During the period of L-NAME administration, both OVI and OVX animals developed hypertension. Upon withdrawal of L-NAME, the hypertension persisted in OVX animals given VEH. However, blood pressure returned to control levels in both OVX animals given E2 and in OVI animals. These results suggest that estrogen in developing female BHR does not protect against the development of L-NAME-induced hypertension, but in the absence of L-NAME, it can reverse the persistent hypertensive state otherwise produced in OVX females.

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