title: AE0047, a new dihydropyridine Ca2+ entry blocker, inhibits the responses to adrenergic nerve stimulation and substance P in dog mesenteric arteries.
abstract: AE0047, a new dihydropyridine-type Ca2+ entry blocker, significantly inhibited the contractions induced by transmural electrical stimulation and norepinephrine in dog mesenteric artery strips. The inhibition was greater in the case of the response to nerve stimulation. The 3H-overflow ratio evoked by electrical stimulation from strips previously soaked in [3H]norepinephrine was significantly reduced by AE0047 but not by nicardipine in a concentration sufficient to attenuate the response to norepinephrine. In aorta homogenate preparations, [3H]bunazosin binding was not replaced by AE0047 but by phentolamine. In strips treated with indomethacin, the endothelium-dependent relaxation caused by substance P and bradykinin was attenuated by treatment with AE0047 but not with nicardipine. The nitric oxide (NO)-induced relaxation was not influenced by AE0047. Cyclic GMP levels in the artery strips increased in response to substance P; the increase was markedly suppressed by AE0047 but not by nicardipine. In contrast to nicardipine, AE0047 appeared to inhibit the release of norepinephrine from adrenergic nerves and of NO from endothelial cells. The inhibition may be associated with the decreased transmembrane influx of Ca2+ in these tissues.
authors.affiliation: Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okamura
authors.forename: M
authors.initials: M
authors.lastname: Nishikawa
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: N
authors.initials: N
authors.lastname: Toda
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006152:Cyclic GMP / Q000032:analysis; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014316:Tritium; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014316:Tritium; C064970:AE0047; D013373:Substance P; D009529:Nicardipine; D006152:Cyclic GMP