The involvement of endothelium‐derived relaxing factor in the regulation of renal cortical blood flow in the rat

1 In the present study the role of endogenous nitric oxide (NO) was investigated, in the regulation of renal cortical blood flow (RCBF) in vivo in anaesthetized rats under conditions in which prostacyclin involvement had been eliminated. 2 Infusions of the NO synthesis inhibitor N G ‐monomethyl‐ l ‐arginine (MeArg) at 1 or 3 mg kg −1 min −1 , i.v., produced significant decreases in RCBF of 29 ± 7% and 35 ± 5%, respectively. These effects were reversed by co‐infusion of a 3 fold excess of l ‐arginine ( l ‐Arg). 3 Similarly, intravenous infusion of N ω ‐nitro‐ l ‐arginine methyl ester (NO 2 Arg) at 30 or 300 μg kg −1 min −1 attenuated RCBF by 21 ± 4% or 53 ± 4%, respectively, and these effects were reversed by l ‐Arg (3 or 10 mg kg −1 min −1 , i.v.). Most importantly, a low dose of NO 2 Arg (30 μg kg −1 min −1 , i.v.), while having no pressor effect, considerably reduced RCBF, indicating that basal release of NO is important for the maintenance of renal cortical blood flow. 4 MeArg (3 mg kg −1 min −1 , i.v.) or NO 2 Arg (300 μg kg −1 min −1 , i.v.) inhibited endothelium‐dependent acetylcholine (ACh, 10 μg kg −1 min −1 , i.v. for 3 min) increases in RCBF in an l ‐Arg reversible manner, but did not affect endothelium‐independent (dopamine 10 μg kg −1 min −1 , i.v., for 3 min) increases. Endothelin‐1 (1 nmol kg −1 , i.v.), when given as a control for the vasoconstrictor effects of MeArg and NO 2 Arg, produced a slight inhibition of the ACh‐induced increase in RCBF, but this effect was significantly weaker than that produced by MeArg or NO 2 Arg. 5 Our findings suggest that MeArg and NO 2 Arg inhibit basal and ACh‐stimulated release of NO in the renal cortical vasculature. Thus, endogenous NO formation may play an important role in the local regulation of renal cortical blood flow.