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:
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.
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.