EFFECTS OF HALOTHANE AND ISOFLURANE ON CARBON MONOXIDE-INDUCED RELAXATIONS IN THE RAT AORTA

Background: Halothane and isoflurane previously were reported to atten uate endothelium-derived relaxing factor/nitric oxide-mediated vasodil ation and cyclic guanosine monophosphate (cGMP) formation in isolated rat aortic rings. Carbon monoxide has many chemical and physiologic si milarities to nitric oxide. This study was designed to investigate the effects of halothane and isoflurane on carbon monoxide-induced relaxa tions and cGMP formation in the isolated rat aorta. Methods isometric tension was recorded continuously from endothelium denuded rat aortic rings suspended in Krebs-filled organ baths. Rings precontracted with submaximal concentrations of norepinephrine were exposed to cumulative concentrations of carbon monoxide (26-176 mu M). This procedure was r epeated three times, with anesthetics delivered 10 min before the seco nd procedure. Carbon monoxide responses of rings contracted with the s ame concentration of norepinephrine (10(-8) M and 2 x 10(-8) M) used i n the anesthetic-exposed preparations also were examined. The concentr ations of cGMP were determined in denuded rings using radioimmunoassay . The rings were treated with carbon monoxide (176 mu M, 30 s) alone, or carbon monoxide after a 10-min incubation with halothane (0.34 mM o r 0.72 mM). To determine whether the sequence of anesthetic delivery i nfluenced results, vascular rings pretreated with halothane were compa red with non-pretreated rings. Results: Carbon monoxide (26-176 mu M) caused a dose-dependent reduction of norepinephrine-induced tension, w ith a maximal relaxation of 1.51 +/- 0.07 g (85 +/- 7% of norepinephri ne-induced contraction). Halothane (0.34 mM and 0.72 mM) significantly attenuated the carbon monoxide-induced relaxations, but only the high est concentration of isoflurane (0.53 mM) significantly attenuated the carbon monoxide-induced relaxations. Carbon monoxide (176 mu M) signi ficantly increased cGMP content (+88.1 +/- 7.1%) and preincubation of the aortic rings with halothane (0.34 mM and 0.72 mM) inhibited this i ncrease (-70.7 +/- 6.8% and -108.1 +/- 10.6%, respectively). When aort ic rings and carbon monoxide were added simultaneously to Krebs soluti on equilibrated with halothane (0.72 mM), no inhibition of cGMP format ion occurred. Conclusion: Carbon monoxide-induced endothelium-independ ent relaxations of rat aortic rings were decreased by clinically relev ant concentrations of halothane and isoflurane. The carbon monoxide-in duced elevations of cGMP were attenuated by halothane only when the an esthetic was incubated with aortic rings before carbon monoxide treatm ent. The possible clinical significance of the actions of the anesthet ics on this endogenous vasodilator is yet to be determined.