N G-Nitro-l-arginine methyl ester inhibits the effect of an H3-histaminergic receptor agonist on NANC contraction in guinea-pig perfused bronchioles

Abstract

Abstract A role for nitric oxide in the H3-histaminergic agonist-induced inhibition of the non-adrenergic, non-cholinergic (NANC) contraction has been studied in guinea-pig perfused bronchioles. (R)-α-Methylhistamine ((R)-α-MeHA), an agonist for H3 receptors, inhibited the NANC contraction induced by electrical field stimulation. NG-Nitro-l-arginine methyl ester (l-NAME) (50 μm), an inhibitor of nitric oxide synthesis, blocked the effect of (R)-α-MeHA. The effect of l-NAME was reversed by l-arginine (50 μm). l-NAME, l-arginine or (R)-α-MeHA were without effect on exogenous substance P- or neurokinin A-induced contractile responses of the perfused bronchioles. These results show that an H3-agonist inhibited the release of neurotransmitters in NANC nerve endings of guinea-pig perfused bronchioles presumably by production of nitric oxide.