Lidocaine potentiates atrial natriuretic peptide-induced relaxation of bovine tracheal smooth muscle.
The effect of lidocaine on the changes in tension and guanosine 3',5'-cyclic monophosphate (cGMP) content induced by atrial natriuretic peptide (ANP) and nitric oxide (NO) was examined in bovine tracheal smooth muscle preparations contracted with methacholine (0.3 microM). Lidocaine (10 microM) did not affect the methacholine-induced tensions, whereas 100 microM lidocaine significantly (P<0.01) attenuated methacholine-induced ones. Treatment of the tracheal preparations with lidocaine (10 and 100 microM) significantly (P<0.05) augmented the relaxant responses to ANP, whereas the same procedure did not alter the responses to sodium nitroprusside, (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (NOR 3) or 8-bromo-cGMP. Lidocaine (100 microM) enhanced cGMP accumulation induced by ANP (0.1 microM) but not by sodium nitroprusside (0.3 microM). In contrast, mexiletine (100 microM), another class Ib antiarrhythmic, did not affect ANP- and sodium nitroprusside-induced relaxations. These results suggest that lidocaine augments ANP-induced relaxation and cGMP accumulation, probably by modulating activation mechanism of particulate guanylyl cyclase.
Nakahara
T
T
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Tokyo 108-8641, Minato-ku, Japan. nakaharat@pharm.kitasato-u.ac.jp
Yunoki
M
M
Moriuchi
H
H
Sakamato
K
K
Ishii
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D004347:Drug Interactions; D004357:Drug Synergism; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D016210:Methacholine Chloride / Q000494:pharmacology; D008801:Mexiletine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D016210:Methacholine Chloride; D009599:Nitroprusside; D008801:Mexiletine; D009320:Atrial Natriuretic Factor; C061872:FK 409; D008012:Lidocaine; D006152:Cyclic GMP