Mechanism of decreased pressor responsiveness to ANG II, NE, and vasopressin in pregnant rats.
The mechanism of decreased pressor responsiveness to pressor agents was examined serially throughout pregnancy in conscious rats. Rats, 15 and 20 days pregnant, showed marked blunting of the pressor response to graded doses of angiotensin, whereas after only 5 days of pregnancy there was a normal response and at 10 days an intermediate pressor response. A role for prior occupancy of vascular angiotensin II receptors for the blunted pressor response was made less likely by the observation that treatment with captopril to decrease endogenous angiotensin II did not improve the angiotensin II pressor response in 15-day pregnant rats. Studies of smooth muscle receptor binding of angiotensin II showed that, in pregnancy, receptor affinity and number was not changed. Inhibition of prostaglandin synthesis with meclofenamate increased the pressor response to angiotensin II toward normal in pregnant animals. The blunted vascular response in pregnancy was not specific for angiotensin since pregnant animals showed a similar decrease in the response to both norepinephrine and arginine vasopressin. Furthermore, meclofenamate increased the pressor response to norepinephrine and vasopressin in pregnant rats. We conclude that pressor hyporesponsiveness in pregnancy is not specific for angiotensin II and is not caused by alterations in vascular receptor occupancy or binding. In pregnancy there is a decreased pressor response to all three major pressor agents that is improved by inhibition of prostaglandin production.
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D005260:Female; D008469:Meclofenamic Acid / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011311:Pressoreceptors / Q000187:drug effects*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology*
D011453:Prostaglandins; D011945:Receptors, Angiotensin; D014667:Vasopressins; D000804:Angiotensin II; D001127:Arginine Vasopressin; D008469:Meclofenamic Acid; D002216:Captopril; D009638:Norepinephrine