Nitroglycerin-induced release of calcitonin gene-related peptide from sensory nerves attenuates the development of nitrate tolerance.

摘要: The present study was designed to determine if endogenous calcitonin gene-related peptide (CGRP) affects the process of nitrate tolerance development in blood vessels. Rat aortic rings were suspended organ chambers and relaxations nitroglycerin (10 -9 -10 -6 M) obtained tolerant nontolerant contracted with norepinephrine -7 M). Tolerance induced by incubating (tolerant) or without (nontolerant) -4 for 90 minutes, followed repeated rinsing 1 hour. Some treated CGRP 8-37 M), glyburide iberiotoxin during 90-minute desensitization period then washed out 1-hour period. Other capsaicin -5 prior Calcitonin release measured radioimmunoassay. Relaxation markedly reduced rings, as compared nontolerant. Incubation specifically resulted even greater impairment response though antagonist had been before completion dose-response curve. Similar results following depletion stores sensory nerves treatment nitroglycerin. Prior no effect on rings. but not period, mimicked suggesting a role K ATP channels peptide. Nitroglycerin caused than twofold increase over basal levels which abolished These suggest that releases from nitrovasodilators, interference either action this enhances extent occurs. finding nitroglycerin-induced attenuates desensitizing represents heretofore unknown event tolerance, demonstrates novel vasculature.