Synergistic Coronary Vasoconstriction Produced by Endothelin-1 in Combination with 5-Hydroxytryptamine

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Abstract
The present study was undertaken to examine the action of endothelin-1 (ET-1) per se, or the combined effects of ET-1 with vasoconstrictor agonists such as acetylcholine (ACh), histamine (His), and 5-hydroxytryptamine (5-HT), all of which have been implicated in the genesis of coronary spasm. Isometric tension development and the cytosolic Ca2+ concentration [( Ca2+]i) in a ring segment of porcine coronary artery loaded with fura-2 were measured simultaneously with a mechanoelectric transducer and a fluorometer, respectively. ET-1 (30-100 pM) specifically potentiated the 5-HT-induced contraction without causing a significant increase in [Ca2+]i. This effect of the peptide seems to be qualitatively similar to that produced by the tumor-promoting phorbol ester, DPB. These results suggest that the combined stimulation of ET-1 and 5-HT augments the Ca2+ sensitivity of the contractile elements through the possible activation of protein kinase C.

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