EFFECT OF NITRIC-OXIDE ON RENIN SECRETION .2. STUDIES IN THE PERFUSEDJUXTAGLOMERULAR APPARATUS

To examine the possible role of NO in macula densa control of renin se cretion, we examined the effects of varying NO availability on renin r elease in the isolated perfused rabbit juxtaglomerular apparatus (JGA) . Gradual increments of luminal Na/Cl concentration ratio (mM/mM) from 26/7 over 46/27, 66/47, to 86/67 caused a progressive decrease in ren in secretion from (as log of nano-Goldblatt hog units vs. time, i.e., log nGU/min) 1.09 +/- 0.34 to 0.46 +/- 0.24 log nGU/min, with the grea test change occurring at the first concentration step. The presence of 0.7 mM N omega-nitro-L-arginine (NNA), an NO synthase inhibitor, in t he luminal fluid significantly reduced renin secretion at the lowest N a/Cl concentration ratio to 0.65 +/- 0.32 log nGU/min (P < 0.01 compar ed with control). Renin secretion at the higher Na/Cl concentration ra tios was not significantly affected by NNA compared with control. In c ontrast to these results, the addition of the NO donor nitroprusside ( 1 mM) to the bath caused a reduction in renin secretion from 1.0 +/- 0 .39 to 0.47 +/- 0.46 log nGU/min (P < 0.05), an effect that was revers ed by bath addition of 0.01 mM methylene blue. Similarly, addition of L-arginine (0.7 mM) to the bath reduced renin secretion from 0.99 +/- 0.37 to 0.81 +/- 0.38 log nGU/min (P < 0.01), whereas addition of L-ar ginine to the luminal fluid increased renin secretion from 0.85 +/- 0. 43 to 1.94 +/- 0.46 log nGU/min (P < 0.05). The stimulatory effect of luminal L-arginine was reversed by the luminal addition of NNA. The pr esent results indicate that an increase in NO generation in the vicini ty of the JGA can cause both an inhibition and a stimulation of renin secretion. The dependence of the directional change of renin secretion on the sidedness of drug application is consistent with the notion th at NO originating from different cellular sources may exert different effects on granular cell renin release.