Volatile and intravenous anesthetics selectively attenuate the release of endothelium-derived hyperpolarizing factor elicited by bradykinin in the coronary microcirculation.

Abstract

In addition to nitric oxide (NO) and prostacyclin (PGI2) another endothelium-derived factor, which hyperpolarizes vascular smooth muscle cell via activation of K+ channels, contributes to the vasorelaxant effect of bradykinin in different vascular beds. Preliminary findings suggest that this endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation is attenuated by both volatile and intravenous anesthetics. Since EDHF may play an important role in the coronary microcirculation, we investigated the effects of isoflurane (2 vol.% equivalent to approximately 250 microM), etomidate (30 and 100 microM), phenobarbital (100 microM) and thiopental (30 and 100 microM) on the EDHF-mediated dilator response to bradykinin and on the endothelium-independent dilatation evoked by sodium nitroprusside (SNP) in the isolated saline-perfused rat heart (Langendorff preparation). None of the anesthetics tested affected the dilator response to bradykinin or SNP under basal conditions. However, following inhibition of NO and PGI2 formation with NG-nitro-L-arginine (100 microM) and diclofenac (1 microM) respectively, isoflurane, etomidate and thiopental, but not phenobarbital, significantly attenuated the NO/PGI2-independent, i.e. EDHF-mediated dilator response to bradykinin, while the vasorelaxant effect of SNP remained unaffected. Isoflurane, etomidate and thiopental, but not phenobarbital, display cytochrome P450-inhibiting properties, suggesting that these anesthetics impair the cytochrome P450-dependent synthesis of EDHF in the coronary microcirculation.