Effects of five different airway smooth muscle relaxants on inhibitory neurotransmission in isolated guinea-pig trachea in vitro

Abstract

Pharmacodynamic effects produced by terbutaline (10 nM), theophylline (10 μM), sodium nitroprusside (30 nM), levcromakalim (0.3 μM) or isradipine (1 nM) on frequency-dependent relaxations induced by electric field stimulation of either proximal or distal parts of isolated guinea-pig trachea were studied in vitro. Preparations were depleted for tachykinins by capsaicin, pretreated with atropine (0.1 μM) and contracted by histamine (2 μM). Drug effects were studied in preparations with combined adrenergic and inhibitory non-adrenergic non-cholinergic (NANC) innervation and in preparations with inhibitory NANC innervation either with or without additional treatment with N G-nitro- l-arginine methyl ester ( l-NAME) (100 μM). In preparations with combined adrenergic and inhibitory NANC innervation terbutaline, sodium nitroprusside, levcromakalim and isradipine significantly reduced relaxant responses to electric field stimulation in proximal preparations, whereas distal preparations were only affected by terbutaline. In preparations with inhibitory NANC innervation without l-NAME pretreatment, terbutaline significantly enhanced relaxant responses to electric field stimulation only in distal preparations, whereas theophylline, sodium nitroprusside and levcromakalim significantly augmented responses to electric field stimulation in both proximal and distal preparations. In preparations with inhibitory NANC innervation pretreated with l-NAME, theophylline significantly inhibited relaxant responses in distal preparations, whereas sodium nitroprusside, levcromakalim and isradipine significantly augmented relaxant responses to electric field stimulation in proximal preparations. It was concluded that drugs used in the present study can modulate the effects of inhibitory autonomic and NANC neurotransmission in isolated guinea-pig trachea. Furthermore, it was shown that some variation in drug effects exists in relation to proximal and distal parts of guinea-pig trachea.