A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation.
Microsomal fractions from arterial walls of pigs and rabbits and fundus of rat stomach generate from prostaglandin endoperoxides (PGG2 or H2) an unstable substance, prostaglandin X (PGX) which is a potent inhibitor of platelet aggregation induced by several different substances. Other microsomal fractions including corpus of stomach, lung and ram seminal vesicles generate smaller amounts of PGX from PGG2 or PGH2. Incubation of microsomes from arterial wall or fundus of stomach with platelet-rich plasma under various conditions shows that the enzyme which generates PGX can utilize endoperoxides liberated from platelets or added to the cuvette, thereby preventing, interrupting or reversing the process of platelet aggregation. The generation of PGX is strongly inhibited (IC50 0.43 mug/ml) by 15-hydroperoxy arachidonic acid. These observations are important in the interpretation of vascular diseases such as atherosclerosis and thrombosis and provide a rational basis for the use of anti-oxidants in the prevention and treatment of these diseases.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D012756:Sheep; D013552:Swine
D001095:Arachidonic Acids; D010545:Peroxides; D011453:Prostaglandins; D012701:Serotonin; D000244:Adenosine Diphosphate; D006899:Mixed Function Oxygenases; D011451:Prostaglandin-Endoperoxide Synthases; D004837:Epinephrine