Anesth Analg 1999;89:49
© 1999 International Anesthesia Research Society
CARDIOVASCULAR ANESTHESIA
Halothane Attenuates Nitroglycerin-Induced Vasodilation and a Decrease in Intracellular Ca2+ in the Rat Thoracic Aorta
Hideaki Tsuchida, MD,
Satoru Tanaka, MD,
Sumihiko Seki, MD,
Hikaru Inoue, MD, and
Akiyoshi Namiki, MD, PhD
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan
Address correspondence and reprint requests to Hideaki Tsuchida, MD, Department of Anesthesiology, Kanazawa Medical University, Daigaku 1-1, Uchinada, Kahoku, Ishikawa 920-0293, Japan. Address e-mail to tsuchida{at}kanazawa-med.ac.jp
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 108 M norepinephrine, followed by endothelium-independent vasorelaxation with nitroglycerin 107 and 106 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 107 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.
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