Effects of Aging on Contraction and Ca2+ Mobilization in Smooth Muscle Cells of the Rat Coronary Artery
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概要
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The present study was undertaken to investigate agonist-induced contraction and Ca2+ mobilization in the smooth muscles of coronary arteries isolated from young (16 weeks) and aged (more than 72 weeks) rats. Ring segments of the rat coronary anterior descending arteries without endothelium were loaded with 40 ?mol/L fura-2 acetoxymethyl ester and mounted in an organ bath. Isometric tension was recorded using a force displacement transducer, and the percentage of phosphorylated myosin light chain (MLC20) was measured with Western blotting. Administration of vasoactive substances such as 5-hydroxytryptamine (5-HT), prostagrandin F2a, histamine, endothelin-1 and angiotensin II (A-II) caused dose-dependent contraction in the isolated coronary arteries, and the active tension (mN force/mg tissue weight) evoked by these agonists was significantly greater in the young rats than in the aged ones. On the other hand, the increase in cytoplasmic calcium ([Ca2+]i) induced by the maximum concentration of the agonists was not significantly different between the 2 groups. The percentage of phosphorylated MLC20 induced by a maximum concentration of 5-HT or A-II was significantly greater in the young rats than in the aged ones. The number of nuclei per medial area was fewer in the aged rats than in the young ones. These results suggest that the age-dependent decrease in the agonist-induced contraction of rat coronary arteries is attributable to a reduction of smooth muscle density in the media and/or an impairment in the signal transduction pathway of the smooth muscle cells. One possible site for the impaired pathway is either downstream from the [Ca2+]i increase or in some Ca2+ independent secondary mechanisms.