Volatile anesthetics exert direct depressant and vasodilator effects on vascular smooth muscle. These effects may result in clinically relevant hemodynamic changes. However, the mechanism is not well known whereby volatile anesthetics inhibit the vasoconstrictor actions of catecholamines at vascular smooth muscle.

The present study examined the direct effects of isoflurane on responses of isolated rabbit thoracic arteries to the norepinephrine(a mixed alpha1- and alpha2-adrenoceptor agonist) and phenylephrine(a selective alpha1-adrenoceptor agonist) applied exogenously. The role of extra- and intracellular Ca2+ in norepinephrine-induced contractions was also examined.

Norepinephrine and phenylephrine produced maximal responses of about the same magnitude; however, norepinephrine was more potint than phenylephrine. Isoflurane depressed only the upper portion(10(-5)~10(-4)M) of norepinephrine dose-response curves. The depression of contraction caused by isoflurane on the dose-response curves of norepinephrine and phenylephrine was more marked with phenylephrine than with norepinephrine; isoflurane(2~3%) caused a concentration-dependent attenuatian of the responses evoked by 10(-5) to 10(-3)M phenylephrine. Ryanodine(a selective inhibitor of sarcoplasmic reticulum Ca2+ channels) attenuated the contractile response to norepinephrine. In the Ca2+-free medium the contractile response to norepinephrine was attenuated as compared to control.

Theses results suggest that isoflurane attenuates the contractile responses of isolated rabbit thoracic arteries to norepinephrine and phenylephrine probably interfering with postjunctional alpha1-receptor function.