Role of angiotensin II in the renal effects induced by nitric oxide and prostaglandin synthesis inhibition.

The objective of this study was to examine the renal effects of changes in intrarenal angiotensin II levels during the administration of a cyclooxygenase inhibitor, when nitric oxide synthesis is reduced. In the first group of dogs, the administration of meclofenamate and a subpressor dose of L-NAME induced an increase (P < 0.05) in arterial pressure (14 +/- 2 mm Hg), a decrease (P < 0.05) in RBF (180 +/- 13 to 111 +/- 10 mL/min) and GFR (37 +/- 3 to 24 +/- 5 mL/min), and a reduction in the renal excretory response to a sodium load. In the second group, the administration of a converting enzyme inhibitor prevented the increase in arterial pressure, the renal vasoconstriction, and the increase in the proximal but not the distal tubular sodium reabsorption induced by the inhibition of prostaglandins and nitric oxide synthesis. In the third group, it was found that a small increase in the intrarenal angiotensin II levels, which does not produce changes in renal function in control conditions, induced a significant decrease in RBF (183 +/- 14 to 71 +/- 12 mL/min) and GFR (36 +/- 3 to 13 +/- 4 mL/min) when meclofenamate was administered and nitric oxide synthesis was slightly reduced. The results of this study suggest that renal vasoconstriction and increased proximal sodium reabsorption during the reduction of nitric oxide and prostaglandin synthesis are produced by endogenous angiotensin II levels. These results also suggest that endogenous intrarenal nitric oxide and prostaglandins may serve as homeostatic mediators of angiotensin II effects when the intrarenal levels are inappropriately elevated, as occurs in salt-sensitive hypertension.