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KMID : 0376219870240010079
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Chonnam Medical Journal
1987 Volume.24 No. 1 p.79 ~ p.91
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Studies on Relaxing Effect of Organic Nitrates on Vascular Smooth Muscle
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Abstract
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To investigate the mechanism of relaxing effects of organic nitrates on isolated porcine coronary arteries, we studied effects of nitroglycerin and isosorbide dinitrate (ISDN) on KCl- and histamine-induced contractions. The calcium channel blocking agent, diltiazem, served as a comparative standard in all experimental protocols. Under resting tension (5.09), 35mM KCl and 35μM histamine produced a remarkable contrac￢tion of porcine coronary rings. a-Adrenoceptor agonists, norepinephrine and clonidine, did not contract the rings even in large dose (10-4M), but norepinephrine caused a transient contraction after treatment with β-adrenoceptor antagonist, propranolol.
Two organic nitrates and diltiazem caused concentration-dependent relaxations of the rings under the resting tension and the potency order was ISDN>diltiazem> nitroglycerin. KCI produced a constant contraction (6.8±2.5g) in normal physiological salt solution (NPSS) but did not produced the contraction at all in 0.5μM free calcium￢physiological salt solution (low free Ca2+-PSS). The KCl-induced contraction was relaxed by three agents in a concentration-dependent manner and was most sensitive to diltiazem. IC50s of diltiazem, nitroglycerin and ISDN were 8 x 10-8M, 4 x 10-6M and 5 X 10-6M, respectively. Histamine produced a relatively constant contraction (9.8±0. 57 :y) in NPSS and caused a transient intracellular calcium-dependent contraction (5.4±)
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