During pregnancy, blood volume increases by 30-40%, although the mechanism(s) by which the increase is maintained is unknown. In normal nonpregnant adults, the baroreceptor reflex plays a very important role in blood volume regulation. In this system increases in blood pressure and blood volume (sensed by stretch receptors located in the heart, carotid sinus, aortic arch kidney) inhibit the production of the volume retaining hormones vasopressin, ACTH and angiotensin II (via renin). Because the increased blood volume of pregnancy appears to be homeostatically maintained, this proposal seeks to test the hypothesis that baroreceptor reflex control of these hormones and other cardiovascular parameters is altered in the pregnant state to maintain the excess volume. In addition, angiotensin II has been shown to participate in baroreflex regulation of blood pressure, heart rate, cardiac output and vasopressin and ACTH secretion.
A second aim of this proposal is to determine, using specific receptor antagonists, whether endogenous angiotensin II affects baroreflex activity in conscious sheep and whether these actions are modified during pregnancy. Finally, in a effort to understand why plasma renin activity is increased with gestation, it will be determined whether changes in the relationship between renal perfusion pressure and renin secretion occur. Baroreflex function will be assessed and compared in pregnant and nonpregnant conscious sheep by examining the relationship between blood pressure and each of the following variables: vasopressin, renin, cortisol and ACTH levels, heart rate, cardiac output and peripheral resistance. Changes in blood pressure will be produced with 30 min infusions of three doses of the vasodilator nitroprusside, or with changes in blood volume caused by hemorrhage. To study the relationship between renal perfusion pressure and renin release sheep will be instrumented with a renal arterial catheter, and occluder and electromagnetic flow probe and a renal venous catheter. Renal arterial pressure will be decreased in 5-10 mm Hg steps for 15 min at which time femoral arterial and renal venous blood samples for renin measurements will be obtained. Curves relating renal arterial pressure to renin secretion will be constructed for pregnant sheep and nonpregnant sheep to determine if renal baroreceptor control of renin release is altered by gestation.
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