EFFECT OF BLOCKADE OF NITRIC-OXIDE SYNTHESIS ON THE RENIN SECRETORY RESPONSE TO FRUSEMIDE IN CONSCIOUS RABBITS

1. The enzyme nitric oxide synthase is present in the macula densa and may participate in the control of renin secretion by the adjacent jux taglomerular cells, In the present study, we investigated the effect o f inhibiting nitric oxide synthase on the renin secretory response to frusemide, which stimulates renin secretion by blocking Na+-K+-2Cl(-) co-transport in the macula densa. 2. Injection of frusemide in 12 cons cious rabbits elicited a transient increase in mean arterial pressure from 84 +/- 2 to 92 +/- 3 mmHg at 5 min (P<0.01) and a sustained incre ase in heart rate from 246 +/- 6 to 281 +/- 10 beats/min at 45 min (P< 0.01), Plasma renin activity increased from 8.0 +/- 1.2 to 14.3 +/- 1. 8, 12.4 +/- 1.6 and 11.6 +/- 1.5 pmol 2h(-1) ml(-1) at 15, 30 and 45 m in respectively (P<0.01), There were no changes in plasma sodium and p otassium concentrations or osmolality. 3. Inhibition of nitric oxide s ynthase with N-G-nitro-L-arginine methyl ester increased mean arterial pressure by 9 mmHg, decreased heart rate and plasma renin activity, a nd markedly suppressed the renin response to frusemide (from 4.6 +/- 0 .7 to 7.6 +/- 1.7, 4.7 +/- 1.0 and 4.6 +/- 0.7 pmol 2h(-1)ml(-1) at 15 , 30 and 45 min respectively), By contrast, infusion of an equipressor dose of phenylephrine did not suppress the renin response to frusemid e. 4. Histochemical studies with the NADPH diaphorase technique confir med the presence of nitric oxide synthase in the macula densa, and sug gested that enzyme activity is increased by treatment with frusemide. 5. These results are consistent with a role for the L-arginine-nitric oxide pathway in the modulation of renin secretion by the macula densa .