Anesthetics alter relative contributions of NO and EDHF in rat cremaster muscle microcirculation

The contributions of the vasodilators nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) were investigated in the rat cremaster muscle microcirculation during halothane, isoflurane, or ketamine anesthesia. After inhibition of prostaglandin synthesis with indomethacin, changes in diameter of fourth-order arterioles to acetylcholine (ACh) or bradykinin (BK) were studied in the presence or absence of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, and/or 20 mM K+, an inhibitor of EDHF action. L-NMMA inhibited ACh- and BK-induced vasodilation during isoflurane but not halothane or ketamine anesthesia. Superfusion of the muscle with buffer containing 20 mM K+ dilated arterioles. EDHF was responsible for most of the NO-independent response to ACh, because 20 mM K+ unmasked ACh-stimulated, NO-dependent relaxation during halothane or ketamine anesthesia. However, 20 mM K+ did not inhibit BK-induced vasodilation during halothane or ketamine anesthesia. Our data suggest that anesthetics can alter the balance between NO and EDHF vasodilation in the microcirculation and that NO-dependent mechanisms are enhanced and EDHF action inhibited during isoflurane anesthesia.