Actions of a newly synthesized nitro-compound, E-4701, on rabbit vascular smooth muscles.

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The effects of a newly synthesized water soluble and light resistant nitrocompound, 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=40μM) 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 μM 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. E4701 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.
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