Captopril as a modifier of the arachidonate cascade of rat platelets.
The lipoxygenase pathway of arachidonate cascade in the platelets of spontaneously hypertensive rats has been found to be significantly higher than in normotensive animals. Repeated oral administration of Captopril (in drinking water - 200 mg/100 ml) for 14 days resulted in an elevation in the activity of arachidonate cascade in the platelets of treated rats. At the same time the Captopril treatment induced the formation of 12-hydroxy-heptadecatrienoic acid (12-HHT), which molecule is known to be a potent prostacyclin (PGI2) releaser and/or synthesis inducer. PGI2 is one of the most potent vasodilatator molecule in living organisms. The in vitro experiments in rat platelets suggest, that very low doses of Captopril (10(-12) to 10(-10) M) result in a significantly elevated 12-HHT synthesis. Captopril might act through the 12-HHT--PGI2 mechanism, resulting in blood pressure reduction. The lipoxygenase pathway of platelets, the formation of 12-hydroxyeicosatetraenoic acid (12-HETE), was significantly elevated in vitro in the presence of low dose of Captopril (10(-11) and 10(-10) M).
Gecse
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Department of Pathophysiology Albert Szent-Györgyi University Medical School of Szeged, Hungary.
Telegdy
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G
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D006973:Hypertension / Q000097:blood*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012016:Reference Values
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D002216:Captopril; D011464:Epoprostenol