Halothane Attenuates Nitroglycerin-Induced Vasodilation and a Decrease in Intracellular Ca2+ in the Rat Thoracic Aorta

UNLABELLED: Although halothane inhibits endothelium-mediated vasorelaxation, the sites of inhibition remain controversial. Because the cytosolic concentration of Ca2+ (Ca2+i) has crucial roles for tension development, we examined the effects of halothane on nitroglycerin-induced vasorelaxation from the standpoint of Ca2+i. Isolated spiral strips of rat thoracic aorta without endothelium were suspended for isometric tension recordings in a physiologic salt solution. Muscle contraction was evoked with 10(-8) M norepinephrine, followed by endothelium-independent vasorelaxation with nitroglycerin 10(-7) and 10(-6) M. The effects of halothane 1.5% and 3% on nitroglycerin-induced vasorelaxation were evaluated along with the concomitant measurement of Ca2+i using fura-2-Ca2+ fluorescence. In other muscle strips, incremental doses of norepinephrine were administered during halothane exposure to induce contractions comparable to those without halothane. Nitroglycerin dose-dependently reduced norepinephrine-induced muscle contractions, but the decrease in Ca2+i reached a plateau at 10(-7) M, which indicates that nitroglycerin induced Ca2+i-dependent and Ca2+i-independent vasorelaxation. Both concentrations of halothane inhibited nitroglycerin-induced decreases in muscle tension and Ca2+i, not only when the same dose of norepinephrine was used for contraction during halothane exposure, but also at incremental doses of norepinephrine. In conclusion, halothane inhibits nitroglycerin-induced vasorelaxation partly by suppressing Ca2+ changes in the smooth muscle. IMPLICATIONS: We examined nitroglycerin-induced vasorelaxation in the rat thoracic aorta, along with the concomitant measurement of the cytosolic concentrations of Ca2+, and found that halothane attenuated endothelium-independent vasorelaxation by suppressing Ca2+ dynamics in the smooth muscle.