EMBARGOED UNTIL
MONDAY, APRIL 19, 2004
Contact: Donna Krupa
703.967.2751 (cell)
703.527.7357 (office)
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APS Newsroom: April 17-21, 2004
Washington, DC Convention Center
East Registration Area/Flex Unit
Telephone: 202.249.4009
Is There A Relationship
Between Repeated Pregnancies And Increased Cardiovascular Disease?
A new study finds some
evidence in a rat model
Washington, DC – Once upon a time, children may
have come “cheaper by the dozen.” But according to a new study from Canada,
repeated pregnancies can adversely affect the body’s cardiovascular
regulation thereby increasing the risk for cardiovascular disease.
Background
Over 500,000 American women die of cardiovascular
disease each year, making this the leading cause of death and disability
among women. Scientists have studied evidence from previously conducted
population studies suggesting that multiparity (repeated pregnancies) may be
a risk factor for cardiovascular disease. Their findings were supported by
evidence from animal studies which indicated that repeated pregnancies could
adversely affect the cardiovascular system. In rats, it has been reported
that repeated pregnancies are associated with degradation of vascular
elastic tissue and an increase in the incidence of spontaneous
arteriosclerosis of the aorta, and of the mesenteric and renal vascular
beds. It has also been reported that repeated pregnancies attenuate the
production of nitric oxide in the kidney, which results in increased
vasoconstriction in renal blood vessels.
Based on the current literature, a new study was
undertaken to explore the effects of repeated pregnancies on cardiovascular
regulation, specifically control of blood pressure. The researchers
hypothesized that repeated pregnancies would increase the blood pressure
response to exogenous administration of the sympathomimetic phenylephrine,
an adrenaline-like vasoconstrictor, and to acute stress. The researchers
also hypothesized that such an augmented response would be mediated through
increased constriction of resistance arteries in the parous animals,
compared with those which had never given birth.
A New Study
The research findings of a presentation entitled
“Long-term Effects of Parity on Blood Pressure Regulation,” are being
presented. The authors are Vivek Dhawan, Zoe L.S. Brookes, and Susan
Jacobs-Kaufman, who conducted the research at the University of Alberta,
Edmonton, Alberta, Canada. (Dr. Brookes is now with the University of
Sheffield in Sheffield, U.K.) The team will present its findings at the
American Physiological Society’s (APS) (www.the-aps.org)
annual scientific conference, Experimental Biology 2003, being held
April 17-21, 2004, at the Washington, D.C. Convention Center.
Methodology
The study was designed to measure the blood pressure
responses to phenylephrine and to acute stress in conscious age-matched
repeatedly breed (RB) and virgin rats. The RB population consisted of seven
to eight-month old female Long Evans rats which had previously undergone
five pregnancies, but which were now retired from the breeding program.
Mean arterial pressure, systolic blood pressure, and
diastolic blood pressure were continuously monitored in both groups of
conscious rats in a stress-free environment. On the day of the experiment,
baseline blood pressure was recorded for an hour. This was followed by
short-term infusion (over 30 sec) of 1, 3, 10, 30 µg•kg-1 of phenylephrine.
The rats were also exposed to acute stress by directing
a jet of pressurized air towards them for 10 seconds. Changes in blood
pressure and heart rate were continuously recorded and changes in mean
arterial pressure, systolic blood pressure and diastolic blood pressure were
compared.
In addition, vascular reactivity and compliance of
isolated mesenteric (intestinal) arteries were studied using isometric wire
and isotonic pressure myograph system respectively.
Results
The researchers found that multiparous (RB) rats
responded to acute stress and to phenylephrine infusion with a greater
increase in blood pressure than was observed in the virgin animals. Other
key findings included:
·
The pressor response to exogenous phenylephrine was greater in
the RB rats than in the virgins. Since this difference was apparent in both
the systolic and diastolic pressure traces, and since there was no
difference in baroreflex buffering, the investigators concluded that the
increased blood pressure in the parous animals could be attributed primarily
to an increase in total peripheral resistance.
·
Stress induces a sympathetically mediated increase in cardiac
output, as well as vasoconstriction (particularly in the mesenteric vascular
bed), resulting in an increase in mean arterial pressure. Rats which had
previously given birth had a potentiated pressor response (mean arterial,
systolic and diastolic pressures), but similar heart rate responses, when
exposed to acute stress initiated by a jet of pressurized air. Again, this
suggests that the larger increase in blood pressure in the parous rats may
be attributed to a greater increase in total peripheral resistance.
·
Isolated mesenteric arteries from RB rats were more sensitive
to phenylephrine and less compliant than were those from the virgin animals.
This difference in sensitivity was endothelium-dependent, since removal of
endothelium abolished the difference.
Conclusions
Although resting blood pressure of the parous rats was
no higher than that of the virgins, their response to stress and to stress
hormones was augmented. This was due, at least in part, to enhanced
constriction of the mesenteric vascular beds. The mechanisms underlying the
effect of repeated pregnancies on vascular compliance and endothelial
function remain uncertain. However, it could be due to resetting of the
hormonal system of the animal after pregnancy; previous studies report that
pregnancy permanently reduces plasma levels of prolactin and estrogen, both
of which have well established effects on the cardiovascular system.
Caveat
The value of this study is clear. The
pregnancy-associated changes observed in rats are very similar to those
found in humans. The advantage of such animal-based studies is that the
experimental conditions can be well controlled, that repeated pregnancies
can be induced in the animals within a short interval of time, and that
blood vessels can be removed and studied for their reactivity. Thus, it was
demonstrated in the rat that repeated pregnancy increases the blood pressure
response to acute stress and to intravenous infusion of phenylephrine. This
was due, at least in part, to changes in both the passive and active
characteristics of the mesenteric blood vessels. The investigators propose
that this could lead to transient stress-induced increases in total
peripheral resistance and cardiac afterload which, in time, could contribute
to the increased risk for cardiovascular disease observed in women who have
several children.
- end -
The
American Physiological Society (APS) was founded in 1887 to foster basic and
applied science, much of it relating to human health. The Bethesda, MD-based
Society has more than 11,000 members and publishes 3,800 articles in its 14
peer-reviewed journals every year.
***
Editor’s
Note: For further information or to schedule an interview with a member of
the research team, please contact Donna Krupa at 703.967.2751 (cell),
703.527.7357 (office) or at
djkrupa1@aol.com. Or contact the APS newsroom at 202.249.4009 between
9:00 AM and 6:00 PM EDT April 17-21, 2004.
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