Insulin-induced attenuation of noradrenaline-mediated vasoconstriction in resistance arteries from Wistar rats is nitric oxide dependent.
1. We studied the mechanism of insulin-mediated attenuation of noradrenaline-induced vasoconstriction in mesenteric resistance arteries (approximately 210 microns diameter) from 10-week-old male Wistar rats (n = 10; weight 321 +/- 11 g). Exposure to physiological concentrations of insulin (50 m-units/l) significantly blunted the contractile response to noradrenaline over the concentration range 3 x 10(-6) to 3 x 10(-5) mol/l (16 vessels; 13.1 +/- 4.3% reduction in maximum tension at 3 x 10(-5) mol/l noradrenaline; P < 0.01 versus no insulin). 2. This effect of insulin was prevented by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (10(-4) mol/l; 16 vessels; 3.3 +/- 9.1% reduction in maximum tension; P = 0.8 versus no insulin). There was no evidence of fatigue in four noradrenaline dose-response curves for 16 control vessels in the absence of insulin and NG-nitro-L-arginine methyl ester (P = 0.8; first versus second dose-response curve). With L-arginine present in the incubation medium, insulin again attenuated the noradrenaline-induced vasoconstriction (10.7 +/- 3.2% reduction in tension; P = 0.02 versus L-arginine and no insulin; P = not significant versus insulin and no L-arginine). 3. Endothelium-dependent relaxation was initially confirmed in all vessels by demonstrating normal acetylcholine- (5.4 x 10(-7) to 1.1 x 10(-4) mol/l) induced vasodilatation in vessels preconstricted with noradrenaline (6 x 10(-6) mol/l) in the absence of NG-nitro-L-arginine methyl ester, L-arginine and insulin (P = not significant between the different groups of vessels). 4. We conclude that insulin attenuates noradrenaline-induced vasoconstriction in resistance arteries by stimulation of nitric oxide release. Abnormal insulin-stimulated nitric oxide release could be of relevance in the pathogenesis of hypertension and diabetic microvascular disease.
Walker
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AB
Department of Medicine, University of Liverpool, U.K.
Savage
M W
MW
Dores
J
J
Williams
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D007328:Insulin; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine