VASOPRESSIN, ACTH AND RENIN SECRETION DURING PREGNANCY

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.