Cardioprotective actions of thromboxane receptor antagonism in ischemic atherosclerotic rabbits.
Atherosclerosis was induced in New Zealand White rabbits by feeding them a 0.5% cholesterol-enriched rabbit chow for 10-12 wk. Half of the cholesterol-fed rabbits were given BM 13505, a specific thromboxane A2/endoperoxide (TxA2/PGH2) receptor antagonist, and the other half were given its vehicle (i.e., 2% Na2CO3). At the end of 10-12 wk, the rabbits underwent experimental myocardial ischemia or an identical sham operation, except that the coronary artery was not occluded. BM 13505 was shown to protect the ischemic rabbit myocardium by three different methods: 1) maintenance of myocardial tissue creatine kinase (CK) activity in the ischemic myocardium; 2) reduced loss of free amino nitrogen-containing compounds from the myocardium; and 3) blunting the rise of plasma CK activity. Part of the mechanism for these effects may be due to inhibition of platelet aggregation and blockade of the vasoconstrictor effect of TxA2. However, these protective effects were not due to differences in myocardial oxygen demand among the groups. Finally, BM 13505 exhibited an antiatherogenic effect by reducing the deposition of cholesterol in the aortic wall and by retarding plaque formation in coronary arteries. However, it does not achieve this antiatherogenic effect by lowering plasma cholesterol concentrations or by scavenging superoxide free radicals. Thus blockade of TxA2 receptors exerts a variety of beneficial effects that reduce the severity of ischemic damage resulting from myocardial ischemia.
Osborne
J A
JA
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Lefer
A M
AM
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000473:pathology; D003402:Creatine Kinase / Q000097:blood; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D012016:Reference Values; D013449:Sulfonamides / Q000494:pharmacology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D002791:Cholesterol, Dietary; D010648:Phenylacetates; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013931:Thromboxanes; D002784:Cholesterol; D003402:Creatine Kinase; C051762:daltroban