Multiple actions of halothane on contractile response to noradrenaline in isolated mesenteric resistance arteries.
Halothane, a volatile anaesthetic, produces systemic hypotension and significantly alters organ blood flow. Isometric force was recorded in isolated rat small mesenteric arteries to investigate its action on contractile response to noradrenaline, the sympathetic neurotransmitter. Halothane (1-5%) enhanced contractile response to noradrenaline in the endothelium-intact arteries, but had little influence in the endothelium-denuded arteries. However, halothane consistently inhibited the noradrenaline response in the endothelium-denuded arteries pretreated with ryanodine (10 microM). The enhancement of the contractile response to noradrenaline in the endothelium-intact arteries was unaffected by treatment with N(G)-nitro L-arginine, tetraethylammonium, apamin, charybdotoxin, indomethacin, diclofenac, nordihydroguaiaretic acid, BQ-123, BQ-788, losartan, ketanserin, or superoxide dismutase. Halothane prolonged vasorelaxation after washout of noradrenaline in the endothelium-denuded arteries. Both ryanodine and vanadate (0.1-0.3 mM), a putative inhibitor of the plasma membrane Ca2+-ATPase, also prolonged the vasorelaxation. Halothane still prolonged the vasorelaxation in the ryanodine-treated arteries, but not in the vanadate-treated arteries. Halothane decreased the pD2 value for the pCa-force relation in the beta-escin-permeabilised, endothelium-denuded arteries. Halothane appears to influence contractile response to noradrenaline through multiple actions including endothelium-dependent enhancing, endothelium-independent enhancing, and endothelium-independent inhibitory actions. Nitric oxide, endothelium-derived hyperpolarising factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin-II, serotonin, and superoxide anions are not involved in the endothelium-dependent enhancement. The endothelium-independent enhancement is presumably due to its ability to stimulate Ca2+ release from the ryanodine-sensitive intracellular stores, while the endothelium-independent inhibition is due, at least in part, to depressed Ca2+-activation of contractile proteins. Halothane may inhibit the plasma membrane Ca2+-ATPase of vascular smooth muscle cells.
Yoshino
J
J
Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Akata
T
T
Izumi
K
K
Takahashi
S
S
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D014662:Vasoconstrictor Agents; D006221:Halothane; D009638:Norepinephrine