Thromboxane in sudden death.
Thromboxane has characteristics that signify potential importance in cardiovascular disease states. In models developed for studying thrombotic sudden death, thromboxane appears to be an important mediator. Thus, in arachidonic acid-induced sudden death, agents that either inhibit thromboxane generation or block thromboxane receptor activation prevent the occurrence of thrombotic death. Thromboxane mimetics are also useful in modeling sudden death; when injected i.v., these compounds elicit effects similar to those obtained with arachidonic acid. In this case, however, pretreatment with cyclooxygenase or thromboxane synthetase inhibitors confers no protection, whereas the thromboxane receptor antagonist retains its efficacy. Other factors that affect susceptibility to experimental sudden death include gender, species, and endocrine status. Thrombotic sudden death models have now been used to test, in vivo, the in vitro antiplatelet aggregatory effect of calcium-channel blockers. The data suggest that dihydropyridine agents such as nifedipine and nisoldipine are protective against thrombosis, whereas verapamil may have little such activity. Furthermore, sudden death induced by a variety of thrombotic challenges is prevented by pretreatment with nifedipine. The thrombotic sudden death models currently employed are useful for the in vivo study of the thrombotic process and for the evaluation of agents with potentially thrombotic or antithrombotic properties.
Myers
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Ramwell
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D000787:Angina Pectoris / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000633:toxicity; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002369:Castration; D003643:Death; D004967:Estrogens / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000633:toxicity; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000502:physiology*; D013931:Thromboxanes / Q000502:physiology*
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D004967:Estrogens; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D005938:Glucocorticoids; D008689:Methacrylates; D011450:Prostaglandin Endoperoxides, Synthetic; D013931:Thromboxanes; D016718:Arachidonic Acid; D013739:Testosterone; D013929:Thromboxane B2; D013928:Thromboxane A2; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; C032408:SQ 26536