Coronary Tone Modulation: Formation and Actions of Prostaglandins, Endoperoxides, and Thromboxanes

• DOI: 10.1126/science.831285
• Publication Date: 2006-10-05T16:03:07Z
• Authors: Philip Needleman; Prasad S. Kulkarni; Amiram Raz
• Keywords: Blood Platelets; 0301 basic medicine; Dose-Response Relationship, Drug; Prostaglandins E; In Vitro Techniques; Coronary Vessels; Peroxides; Vasomotor System; Structure-Activity Relationship; 03 medical and health sciences; Species Specificity; Prostaglandins; Animals; Cattle; Rabbits; Hydroxy Acids; Pyrans

Exogenous prostaglandin (PGE2) contracts bovine and human coronary arteries but its precursor, arachidonic acid, relaxes them. The endoperoxides PGH2and PGH3relax bovine coronary strips, but PGH1produces contraction. The primary prostaglandins exert opposite effects to their own endoperoxide precursors, thus, PGE2and PGE3contract, and PGE1relaxes the bovine coronary arteries. The paradoxical coronary dilation produced by the arachidonate or the PGH2suggest that little if any coronary isomerase which converts endoperoxide into PGE2exists, or that a novel, potent, PG-like substance is produced by the isolated coronary arteries. Although the coronaries do not possess thromboxane A2synthetase activity, the vessels are profoundly contracted by exogenous thromboxane A2. Thromboxane A2can be synthesized and released by circulating platelets when they are aggregated by endothelial injury or thrombin. Thus, coronary tone, and possible spasm, in ischemic myocardial zones may be influenced markedly by interplay between prostaglandins, endoperoxides, and thromboxane formed by platelets on the one hand, and endoperoxide products synthesized endogenously in the coronary arteries on the other.