Chemically induced platelet lysis causes vasoconstriction by release of serotonin.
Our previous studies have shown that menadione is cytotoxic to platelets, leading to substantial release of vasoactive substances. To test whether platelet lysis induced by menadione could cause vasoconstriction, we investigated the effect of platelet lysate induced by menadione on rat aorta in organ bath system. We showed that menadione-induced platelet lysate caused vasoconstriction in a dose- and time-dependent manner. These effects were seen in aortic rings both with and without endothelium, but it was much greater in rings without intact endothelium. The time course of vasoconstriction was well correlated with the time courses of platelet lysis (assessed by lactate dehydrogenase release) as well as serotonin release. The vasoconstriction by platelet lysate was blocked by serotonin antagonists, ketanserin, and LY53,857, but not by thromboxane A2 (TXA2) receptor antagonist, SQ29,548, suggesting that vasoconstriction mainly occurred secondary to the release of serotonin in our in vitro system. However, potentiation of vasoconstriction by combined treatment of serotonin and a stable TXA2 mimic, U46619, suggests the possibility of the increased risk for vasoconstriction in vivo. In addition, the serotonin-induced vasoconstriction was potentiated by residual menadione present in the organ bath. These results suggest that chemically induced platelet cytotoxicity can provoke alteration in vasomotor tone by release of serotonin.
Lee
J Y
JY
College of Pharmacy, Seoul National University, Korea.
Lee
M Y
MY
Chung
S M
SM
Chung
J H
JH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004730:Endothelium, Vascular / Q000187:drug effects; D004873:Ergolines / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006490:Hemostatics / Q000633:toxicity*; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014812:Vitamin K / Q000633:toxicity*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004873:Ergolines; D005231:Fatty Acids, Unsaturated; D006490:Hemostatics; D006834:Hydrazines; D010975:Platelet Aggregation Inhibitors; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; D014812:Vitamin K; D012701:Serotonin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D007650:Ketanserin; D007770:L-Lactate Dehydrogenase; C032663:LY 53857