ANGIOTENSIN-II STIMULATES SYNTHESIS OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE

Previous studies have suggested that NO may play an important role in protecting the renal vessels ti om angiotensin II (ANGII)-mediated vas oconstriction. One possible mechanism for this interaction is that ANG II could stimulate NO production in the kidney by increasing endotheli al NO synthase (NOS III). The present studies were performed in rats t o determine whether acute or chronic elevations in ANGII are associate d with enhanced renal NOS III mRNA or protein synthesis. In both acute and chronic studies captopril (20 mu g/kg/min) was given IV to inhibi t endogenous ANGII production. Acute suprarenal infusion of ANGII (8 n g/kg/min) for 110 minutes had no effect on arterial pressure but decre ased GFR and renal plasma now by 20% and 30%, respectively, and increa sed renal vascular resistance by 70%. Acute ANGII increased renal NOS III mRNA by 70% (as determined by ribonuclease protection assay), but had no effect on renal NOS III protein concentration (as detected by W estern blot analyses). In contrast, chronic infusion of ANGII (5 ng/kg /min) for 10 days, increased arterial pressure by 30% and tended to re duce GFR and renal plasma now. Chronic ANGII had no effect on renal NO S III mRNA levels, but increased NOS III protein by 90%. These data su ggest that ANGII can stimulate NOS III synthesis and suggest that this may be one of the mechanisms whereby AngII may enhance NO production.