CHANGES IN ANGIOTENSIN-II METABOLISM CONTRIBUTE TO THE INCREASED PRESSOR-RESPONSE TO ANGIOTENSIN AFTER CHRONIC TREATMENT WITH L-NAME IN THESPONTANEOUSLY HYPERTENSIVE RAT

1. Administration of nitric oxide (NO) synthase inhibitors, such as L- NAME, is associated with an increase in blood pressure and an increase in presser responsiveness to infused angiotensin II (AngII). The pres ent study was designed to investigate the contribution of changes in t he metabolism of AngII to the enhanced presser response to AngII in th e spontaneously hypertensive rat (SHR; 14 weeks old) chronically treat ed with L-NAME. 2. Group I rats received L-NAME for 7 days (5 mg/kg pe r day) in their drinking water. Group II rats received water only. On day 7, rats were anaesthetized and metabolic clearance studies were pe rformed. AngII concentrations in plasma and infusate were measured by radioimmunoassay, 3. Urinary NO2 was unchanged after L-NAME treatment, while NO3 decreased compared with control. Mean arterial pressure (MA P) was higher in the L-NAME treated rats than in control. After 30 min infusion of AngII, MAP increased significantly in both groups, althou gh the increase was larger in L-NAME-treated than control rats. The me tabolic clearance rate of AngII was significantly lower in L-NAME-trea ted rats than in the control group, 4. We conclude that chronic NO syn thase inhibitors, such as L-NAME, cause a decrease in the rate at whic h AngII is metabolized. This decrease, in combination with the increas e in the number of vascular AngII receptors, may account for the repor ted increase in presser responsiveness to infused AngII.