Cyclic GMP-dependent and cyclic GMP-independent actions of nitric oxide on the renal afferent arteriole

1 The effects of exogenous NO and endothelial-derived NO (EDNO) on the afferent arteriole were investigated in the in vitro perfused hydronephrotic rat kidney. Vessels were pre-constricted with angiotensin II (0.1-0.3 nM) or KCl (30 mM). NO was infused directly into the renal artery at concentrations ranging from 30-9000 nM. ODQ (10, 30 mu M) was administered to examine the effects of guanylyl cyclase inhibition. Kidneys were treated with ibuprofen (10 mu M) to avoid actions of prostaglandins. 2 During angiotensin II-induced vasoconstriction, NO elicited vasodilation at concentrations of 30-900 nM (EC(50) = 200 nM) and ODQ caused a 10 fold shift in NO-sensitivity (EC(50) 1600 nM). During KCl-induced vasoconstriction, NO elicited a maximal dilation of 82 +/- 9% at 9000 nM (EC(50) 2000 nM) and ODQ had no effect. Thus in the presence of ODQ, the NO concentration-response curves for KCl- and angiotensin II-induced vasoconstriction were identical (P > 0.2). 3 To assess the possible role of cyclic GMP-independent mechanisms in the actions of EDNO, we compared the effects of L-NAME, ODQ and ODQ + L-NAME. on acetylcholine-induced vasodilation. Angiotensin II reduced afferent arteriolar diameters from 16.7 +/- 0.5 to 8.1 +/- 0.8 microns and acetylcholine fully reversed this effect (16.9 +/- 0.5 microns). ODQ restored the angiotensin II response in the presence of acetylcholine (7.1 +/- 0.6 microns) and the subsequent addition of L-NAME had no further effect (6.8 +/- 0.7 microns). Similarly, L-NAME alone, fully reversed the actions of acetylcholine. 4 Our findings indicate that exogenous NO is capable of eliciting renal afferent arteriolar vasodilation through both cyclic GMP-dependent and cyclic GMP-independent mechanisms. The cyclic GMP-independent action of NO did not require K(+) channel activation. as it could be elicited in the presence of 30 mM KCI. Finally, although cyclic GMP-independent effects of exogenous NO could be demonstrated in our model, EDNO appears to act exclusively through cyclic GMP.