A STUDY OF ANGIOTENSIN II RECEPTORS AFTER CHRONIC INHIBITION OF NITRIC OXIDE SYNTHASE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. Nitric oxide (NO) synthase inhibition, induces a sustained increase in blood pressure and amplifies the pressor response to infused angiotensin II (AngII). This study was designed to investigate the contribution of AngII receptors to the elevated blood pressure and enhanced pressor response to AngII in the spontaneously hypertensive rat (SHR) chronically treated with N^G-nitro-l -arginine-methyl ester (l -NAME). 2. Two groups of 13 week old female SHR were housed four to a box. Group I rats received l -NAME for 7 days (2.5 mg/kg per day) in their drinking water. Group II rats received water only. Blood pressure was monitored daily by tail-cuff plethysmography. Plasma AngII was measured by radioimmunoassay. Aortic and uterine receptor binding was determined by saturation analysis using [¹²⁵I]-Sar⁸, Ile¹)AngII. Data was analysed using the computer program ligand. 3. Mean systolic blood pressure was significantly elevated in rats treated with l -NAME compared with the control group. Plasma AngII concentration was slightly decreased in rats treated with l -NAME compared with control. Densities of both aortic and uterine AngII receptors increased significantly following NO synthase inhibition. Receptor affinity in the aorta decreased in the l -NAME group compared with control. However, uterine AngII receptor affinity was unchanged. 4. We conclude that the increased blood pressure and enhanced pressor responsiveness that occurs with chronic inhibition of NO synthesis may result partly from increased vascular AngII receptor expression.