Modulation of glomerular arteriolar tone by nitric oxide synthase inhibitors.
The inhibition of nitric oxide production has been shown to reduce RBF. The effects of the nitric oxide synthase inhibitors, N omega-nitro-L-arginine and NG-monomethyl-L-arginine, on afferent and efferent arterioles isolated from rabbit kidneys were examined. Under basal conditions, N omega-nitro-L-arginine (10(-7) to 10(-3) M) had no effect on efferent arteriole lumen diameter but caused a 40% decrease in the lumen diameter of afferent arterioles. In afferent and efferent arterioles precontracted with norepinephrine, N omega-nitro-L-arginine and NG-monomethyl-L-arginine (3 x 10(-4) M) markedly attenuated the vasorelaxant effects of the endothelium-dependent vasodilator acetylcholine. In both arterioles, the inhibitory effect of N omega-nitro-L-arginine on acetylcholine-induced relaxation could be reversed by L- but not D-arginine (10(-3) M). However, N omega-nitro-L-arginine had no effect on the relaxation produced by the endothelium-independent vasodilators prostaglandin E2 (afferent) and dopamine (efferent). These observations demonstrate that under the in vitro conditions used in this study, afferent arterioles but not efferent arterioles synthesize and release nitric oxide in the basal state. However, both arterioles release nitric oxide in response to an endothelium-dependent vasodilator. The results of this study provide further evidence for an important role of nitric oxide in the regulation of renal hemodynamics.
Edwards
R M
RM
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Trizna
W
W
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000098:blood supply*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D015232:Dinoprostone; D000109:Acetylcholine; D004298:Dopamine; D009638:Norepinephrine