Attenuation of endothelium-mediated vasodilation by halothane.
To determine whether halothane alters endothelium-mediated vasodilation of vascular smooth muscle, isolated ring preparations of rabbit aorta and canine femoral and carotid arteries were suspended for isometric tension recordings in Krebs-Ringer bicarbonate solution at 37 degrees C. Acetylcholine and bradykinin have been shown to relax these norepinephrine contracted arteries via an endothelium-dependent process. In this study, these relaxations were reversibly and significantly attenuated by 2% halothane. However, halothane did not affect relaxations caused by nitroglycerin, which, in these vessels, acts by an endothelium independent mechanism. These results suggest that halothane is not interfering with cyclic guanylate-monophosphate mediated relaxation of vascular smooth muscle, but may interfere with the synthesis, release, or transport of the endothelium-derived relaxing factor. In addition, during contractions evoked by norepinephrine, halothane caused significant decreases in tension in both the canine carotid and rabbit aortic preparations, but increased tension in the femoral artery rings. These effects were not altered by mechanical removal of the endothelium. These results suggest a direct action of halothane on the vascular smooth muscle, which can result in either an increase or decrease in tension, depending on the specific vessel. In addition to its direct vascular effect, this study suggests a new action of halothane; it interferes with endothelium-derived relaxing factor-mediated relaxation of vascular smooth muscle. This action may contribute in part to the vascular alterations seen clinically during administration of halothane.
Muldoon
S M
SM
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Hart
J L
JL
Bowen
K A
KA
Freas
W
W
D000818:Animals; D001688:Biological Products / Q000378:metabolism; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D001688:Biological Products; D009569:Nitric Oxide; D006221:Halothane