Effect of an arginine analogue on acetylcholine-induced coronary microvascular dilatation in dogs.
The purpose of this study was to elucidate the contribution of endothelium-derived relaxing factor (EDRF) derived from arginine to acetylcholine (ACh)-induced coronary arteriolar vasodilatation in vivo. Experiments were performed in 62 open-chest anesthetized dogs. Internal diameters of small arterioles (less than 120 microns) and large arterioles (greater than 120 microns) were measured using an intravital microscope and stroboscopic epiillumination synchronized to the cardiac cycle. Topically administered NG-monomethyl-L-arginine (L-NMMA, 3 x 10(-4) M) constricted small arterioles (-10.7 +/- 3.1% from control diameter, P less than 0.05), but L-NMMA did not produce vasoconstriction in large arterioles. ACh, in the absence of L-NMMA, caused a dose-dependent vasodilatation in both small and large arterioles. In large arterioles, L-NMMA completely abolished the ACh-induced vasodilatation (10(-5) M topical ACh: from 13.3 +/- 3.0 to -2.0 +/- 1.5%, P less than 0.05; 10(-4) M ACh: from 20.9 +/- 3.9 to -3.0 +/- 1.9%, P less than 0.01). In small arterioles, L-NMMA only partially inhibited the vasodilatation (10(-5) M ACh: from 35.4 +/- 4.0 to 19.0 +/- 2.7%, P less than 0.05; 10(-4) M ACh: from 42.5 +/- 4.8 to 22.6 +/- 3.1%, P less than 0.05). L-Arginine (10(-3) M topically) reversed L-NMMA inhibition of ACh-induced vasodilatation. Persistent dilatation of small arterioles also occurred when NG-nitro-L-arginine rather than L-NMMA was administered.(ABSTRACT TRUNCATED AT 250 WORDS)
Komaru
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Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City 52242.
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D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine