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 change s in intrarenal angiotensin II levels during the administration of a c yclooxygenase inhibitor, when nitric oxide synthesis is reduced. In th e first group of dogs, the administration of meclofenamate and a subpr essor dose of L-NAME induced an increase (P < 0.05) in arterial pressu re (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 i n the renal excretory response to a sodium load. In the second group, the administration of a converting enzyme inhibitor prevented the incr ease in arterial pressure, the renal vasoconstriction, and the increas e in the proximal but not the distal tubular sodium reabsorption induc ed 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 functio n 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 m eclofenamate 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 ni tric oxide and prostaglandin synthesis are produced by endogenous angi otensin II levels. These results also suggest that endogenous intraren al nitric oxide and prostaglandins may serve as homeostatic mediators of angiotensin II effects when the intrarenal levels are inappropriate ly elevated, as occurs in salt-sensitive hypertension.