Nitric Oxide Affects Angiotensin II Pressor Response: Possible Mechanism of Attenuated Pressor Response during Pregnancy and Etiology of Pregnancy-Induced Hypertension

Abstract

Objective: To investigate the mechanism of attenuated pressor responses to several vasoconstrictors during gestation, we sought to characterize the effects of N^G-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) on the pressor response to the infusion of angiotensin II in rats. Methods: L-NMMA and L-Arg were infused intraperitoneally into rats at a constant rate by means of an osmotic minipump. The L-NMMA group received an infusion of L-NMMA (3 mg/day) daily for 13 days, whereas the L-NMMA plus L-Arg group received L-NMMA (3 mg/day) daily for 4 days, followed by L-NMMA plus L-Arg (12 mg/day) daily for 9 days. Sham-operated rats served as controls. The animals were anesthetized on day 13, and catheters were placed into the femoral artery and vein. After the animals had recovered from anesthesia, the pressor response to intravenous bolus doses of angiotensin II (50, 100, 200, and 400 ng/kg) were determined after recovery from anesthesia. Results: While the baseline mean arterial blood pressure was not affected by L-NMMA, with or without L-Arg, the pressor response to angiotensin II in the L-NMMA group was significantly increased as compared with that in the control group, at doses of 50, 100, and 200 ng/kg. The response of the L-NMMA plus L-Arg group did not differ significantly from that of the control group. Conclusion: Results indicate that the infusion of a nitric oxide synthase inhibitor, at a dose insufficient to produce hypertension, increases the pressor response to angiotensin II.