Evidence of a role for compounds derived from arginine in coronary response to serotonin in vivo.
Recent studies have demonstrated that a nitroso compound derived from L-arginine (Arg) may be the endothelium-derived relaxing factor (EDRF) released from vascular endothelium. Synthesis of EDRF from L-Arg is inhibited by analogues of Arg such as NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine (L-NNA). We tested the role of compounds derived from Arg in the constriction of the proximal left anterior descending coronary artery (LAD) to serotonin in vivo by measuring responses before and during infusion of L-NMMA or L-NNA. In open-chest anesthetized dogs the LAD was perfused at constant pressure (80 mmHg) from a reservoir. Large-artery diameter was measured with piezoelectric crystals, and coronary flow was measured with an in-line electromagnetic flow probe. Intracoronary serotonin (5 and 50 micrograms/min) caused a dose-dependent constriction of the proximal LAD and increase in coronary flow. Intracoronary L-NMMA (2 mg/min) or L-NNA (2 mg/min) augmented the constriction to serotonin, whereas the increase in coronary flow was blunted only by L-NNA. L-Arg (10 mg/min, intracoronary) alone did not alter either the large-artery constriction or the increase in flow to serotonin; however, it prevented the enhanced constriction to serotonin following L-NMMA. Constriction to the endothelium-independent agent prostaglandin F2 alpha was not affected by L-NMMA. We conclude that a metabolite of L-Arg modulates the large coronary artery response to serotonin in vivo.
Cappelli-Bigazzi
M
M
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242.
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004338:Drug Combinations; D005260:Female; D008297:Male; D019335:Nitroarginine; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D019323:omega-N-Methylarginine
D004338:Drug Combinations; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D012701:Serotonin; D001120:Arginine; D015237:Dinoprost