5-Hydroxytryptamine potentiates vasoconstrictor effect of endothelin-1.
Interactions between 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) relative to contraction of rat aortic rings were examined in this study. Pretreatment of rings with threshold concentration of 5-HT potentiated the subsequent contractile response to ET-1. However, pretreatment with threshold concentration of ET-1 did not potentiate the contractile response to 5-HT. The 5-HT receptor antagonist LY 53857 blocked the synergistic contractile effects of 5-HT and ET-1 on rat aortic rings. Indomethacin and the thromboxane A2/endoperoxide receptor antagonist SQ 29548 also attenuated (P less than 0.05) the synergistic contractile effects of 5-HT and ET-1, suggesting release of thromboxane A2 or expression of thromboxane A2 receptors during this interaction. The calcium channel blocker verapamil also decreased the synergistic contractile effects of 5-HT and ET-1. Contraction of aortic rings by 5-HT alone was abolished by LY 53857 and attenuated by verapamil, diltiazem, and SQ 29548. Decrease in the force of contraction by verapamil as well as diltiazem indicates activation of voltage-dependent calcium channels during 5-HT-mediated contraction and perhaps during amplification of the vasoconstrictor activity of ET-1 by 5-HT.
Yang
B C
BC
Department of Medicine, University of Florida College of Medicine, Gainesville 32610.
Nichols
W W
WW
Lawson
D L
DL
Mehta
J L
JL
D000818:Animals; D001011:Aorta / Q000187:drug effects; D004357:Drug Synergism; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016232:Endothelins; D014662:Vasoconstrictor Agents; D012701:Serotonin