Endothelin-1 (30-100 pM) selectively potentiated 5-hydroxytryptamine-induced contraction in porcine coronary arteries 1.5 to 2 times over control without significantly increasing cytosolic Ca2+.
Endothelin-1 selectively potentiates 5-HT-induced contraction in porcine coronary arteries, suggesting a functional interaction that modulates calcium sensitivity of contractile elements.
In order to elucidate the physiological and potential pathological roles of endothelin-1 (ET-1) in coronary artery contraction and relaxation, we undertook the present study to examine the action of ET-1 itself, and the combined effects of ET-1 with vasoconstrictor agonists such as acetylcholine (ACh), histamine, and 5-hydroxytryptamine (5-HT), all of which have been implicated in the genesis of coronary spasm. 2. Isometric tension and cytosolic Ca2+ concentration (Ca2+i) in a ring segment of porcine coronary artery loaded with fura-2 were measured simultaneously. 3. ET-1 contracted the artery in a concentration-dependent manner; and nisoldipine, a Ca2+ channel blocking drug of the 1,4-dihydropyridine type, antagonized the ET-1 action non-competitively. A radio-receptor binding assay also indicated the mutually exclusive binding of ET-1 and (+)-3H-PN200-110, a Ca2+ channel ligand, to the membrane fraction of porcine coronary artery. 4. ET-1 (10-100 pM) increased tension and Ca2+i in a parallel manner, while at higher concentrations (1-10 nM) it produced further contraction with a small increase in Ca2+i. 5. ET-1 (30-100 pM) selectively potentiated the 5-HT-induced contraction 1.5 to 2 times over the control without causing a significant increase in Ca2+i, which seems to be qualitatively similar to a tumour promoting phorbol ester, 12-deoxyphorbol 13-isobutylate (DPB). Bay K 8644 (10 nM), on the other hand, potentiated the contraction in response to practically all agonists used and affected a concomitant increase in Ca2+i.6. A Ca2+ channel blocking drug such as diltiazem abolished the increase in Ca2+i and partially attenuated the mechanical potentiation produced by a small amount of ET-1 in combination with 5-HT.7. The results suggest that ET-1 and 5-HT interact functionally at the cellular or subcellular level and modulate the Ca2 + sensitivity of the contractile elements through the possible activation of protein kinase C.
Nakayama et al. (Sun,) conducted a other in Coronary artery contraction. Endothelin-1 (ET-1) vs. Control was evaluated on Isometric tension and cytosolic Ca2+ concentration. Endothelin-1 (30-100 pM) selectively potentiated 5-hydroxytryptamine-induced contraction in porcine coronary arteries 1.5 to 2 times over control without significantly increasing cytosolic Ca2+.
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