Mechanical and electrical properties of smooth muscle cells and their regulations by endothelium-derived factors in the guinea pig coronary artery.

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Effects of high K<SUP>+</SUP>, acetylcholine (ACh), 9, 11 -epithio-1 1, 12-methano-thromboxane A<SUB>2</SUB> (STA<SUB>2</SUB>), thrombin and endothelin were investigated on smooth muscles of the guinea pig coronary artery in intact and endothelium-denuded tissues. In intact tissues, ACh transiently inhibited but ATP produced maintained inhibition of the STA<SUB>2</SUB>-induced contraction. However, in the endothelium-denuded tissue, ACh produced contraction and ATP inhibited the STA<SUB>2</SUB>-induced contraction. In intact tissues, thrombin produced dual actions on the STA<SUB>2</SUB>-induced contraction with an initial relaxation followed by contraction. In endothelium-denuded tissues, thrombin enlarged the STA<SUB>2</SUB>-induced contraction without transient relaxation. In intact tissues prepared from both proximal and distal regions, endothelin showed the same dual action as observed with thrombin, whereas higher concentrations of endothelin showed only contraction. In endothelium-denuded tissues, endothelin consistently produced contraction. In intact tissues prepared from proximal and distal regions, ACh produced a biphasic response (initial hyperpolarization and subsequenty generated depolarization). The amplitudes of both potential changes occurred in a membrane potential-dependent manner. In endothelium-denuded tissues, ACh depolarized the membrane in both tissues. In intact and endothelium denuded tissues, ATP hyperpolarized the membrane in inverse proportion to the membrane potential level, whereas thrombin and endothelin consistently depolarized the membrane. The results indicate that ACh acts on endothelial and smooth muscle cells, and the former releases both EDRF and EDHF. ATP only acts on smooth muscle cells and hyperpolarizes the membrane. STA<SUB>2</SUB>, thrombin and endothelin act on both endothelial and smooth muscle cells. STA<SUB>2</SUB> and endothelin may release EDRF but not EDHF, and thrombin may release EDRF and endothelin.
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