Vasoinhibitory action of KT2-734, an antihypertensive agent, in isolated rat aorta.
In rat aorta, KT2-734 inhibited contractile responses to 5-hydroxytryptamine (5-HT) and KCl. KT2-734 inhibited the relaxing effect of verapamil, but not nifedipine. Similarly, verapamil, but not nifedipine, inhibited the vasorelaxing effect of KT2-734. KT2-734 relaxation was inhibited by endothelium removal but not by atropine and propranolol. Methylene blue, a guanylyl cyclase inhibitor, and NG-monomethyl arginine also inhibited the relaxation both in the presence and absence of endothelium. In the absence of endothelium, KT2-734 potentiated the relaxation induced by L-arginine, nitroglycerin and isoproterenol. In addition, M & B 22,948, a cGMP phosphodiesterase inhibitor, and theophylline inhibited and potentiated, respectively, KT2-734-induced relaxation. However, methylene blue inhibited the potentiation of isoproterenol relaxation by KT2-734 and that of KT2-734-relaxation by theophylline. KT2-734 caused increases in the level of cGMP without significantly affecting the cAMP level. These results suggest that KT2-734 may cause endothelium-independent relaxation mainly due to inhibition of cGMP-phosphodiesterase.
Satake
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N
Department of Pharmacology, School of Medicine, University of Hawaii, Honolulu 96822.
Zhou
Q
Q
Kosakai
K
K
Nimura
M
M
Shibata
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001285:Atropine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007093:Imidazoles; D012702:Serotonin Antagonists; C086489:2-phenyl-8-ethoxycycloheptimidazole; D009569:Nitric Oxide; D001285:Atropine; D011433:Propranolol; D000242:Cyclic AMP; D006152:Cyclic GMP; D008751:Methylene Blue