title: Halothane attenuates nitroglycerin-induced vasodilation and a decrease in intracellular Ca2+ in the rat thoracic aorta.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Sapporo Medical University School of Medicine, Japan. tsuchida@kanazawa-med.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Tsuchida
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Seki
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: A
authors.initials: A
authors.lastname: Namiki
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin; D002118:Calcium; D006221:Halothane