Actions of a newly synthesized nitro-compound, E-4701, on rabbit vascular smooth muscles.
The effects of a newly synthesized water soluble and light resistant nitro-compound, E-4701, on the electrical and mechanical properties of smooth muscle cells of rabbit mesenteric and coronary arteries were investigated. In the endothelium-denuded rabbit mesenteric artery, E-4701 relaxed the tissue pre-contracted by noradrenaline (IC50 = 40 microM) to a greater extent than that contracted by high K, but to a lesser extent than that contracted by acetylcholine (ACh) or high K in endothelium-denuded rabbit coronary artery (the IC50 was 20 nM or 60 nM, respectively). Nitroglycerin showed much the same relaxing action on the above tissue (IC50 for the ACh- or K-induced contraction was 20 nM or 65 nM, respectively). Relaxing actions of E-4701 or nitroglycerin were prevented by 10 microM methylene blue. In muscle cells of the porcine coronary artery, E-4701 or nitroglycerin inhibited the Ca-transient provoked by ACh, as examined using fura-2. Both drugs had no effect on the Ca-induced contraction in skinned muscle strips. ACh produced a transient hyperpolarization with subsequent depolarization, but in the endothelium-denuded tissues. ACh only depolarized the membrane. E-4701 inhibited the ACh-induced depolarization, but nitroglycerin did not. We concluded from our observations that E-4701 has the typical characteristics of a nitrocompound with an inhibitory action on the agonist-induced membrane depolarization.
Satoh
S
S
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Fujiwara
T
T
Nishiye
E
E
Sumimoto
K
K
Itoh
T
T
Suzuki
H
H
Kuriyama
H
H
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology; D011817:Rabbits; D012964:Sodium / Q000502:physiology; D013552:Swine
D004146:Dioxanes; D004147:Dioxins; C062697:E 4701; D012964:Sodium; D005996:Nitroglycerin; D000109:Acetylcholine; D002118:Calcium; D008751:Methylene Blue; D009638:Norepinephrine