Apr 19 2004
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.
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) (http://www.the-aps.org) annual scientific conference, Experimental Biology 2004, 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 µgokg-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.
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