EFFECT OF NITRIC-OXIDE ON RENIN SECRETION .1. STUDIES IN ISOLATED JUXTAGLOMERULAR GRANULAR CELLS

Experiments were performed on juxtaglomerular granular cells (JGC) in short-term primary culture to determine the direct immediate effect of NO on renin secretion and to test whether JGC are able to generate NO . Renin secretion was measured repeatedly over short time intervals in a cell superfusion system. Renin release did not significantly decrea se over a 40-min observation period in untreated JCC. Addition of sodi um nitroprusside (SNP) caused a reduction in renin release (measured i n nano-Goldblatt hog units vs. time, i.e., nGU/min) from 479 +/- 25, 4 23 +/- 70, and 388 +/- 54 nGU/min to 295 +/- 19 (n = 5), 102 +/- 21 (n = 7), and 71 +/- 9 nGU/min (n = 6) with 10(-5), 10(-4), and 10(-3) M SNP, respectively. In the presence of the guanylate cyclase inhibitor methylene blue at 10(-4) M, SNP at 10(-4) M had no significant effect on renin secretion. 8-Bromoguanosine 3',5'-cyclic monophosphate at 10( -4) M in the presence of the phosphodiesterase inhibitor 3-isobutyl-1- methylxanthine (10(-3) M) caused a reduction of renin secretion to 50. 1 +/- 3.6% of control. To examine the possibility that renin secretion is affected by NO release from JGC, we assessed the effect of the NO synthase (NOS) substrate L-arginine (10(-3) M) and the NOS blocker N-o mega-nitro-L-arginine (10(-4) M) on renin secretion. Renin release was not significantly altered by either stimulation or inhibition of NOS activity. The results of these studies demonstrate that exogenous NO a cutely affects JGC and that one result of this direct interaction of N O with JGC is inhibition of renin secretion. Thus the stimulation of r enin release sometimes reported in short-term experiments may reflect interaction of NO with other cell types. The present data are consiste nt with the notion that NO participates in the regulation of renin rel ease.