Additive beneficial effects of two inhibitors of vasoconstrictor mediators in acute myocardial ischemia.
A specific inhibitor of thromboxane A2 (TxA2) synthesis, CGS-12970, a new angiotensin-converting enzyme (ACE) inhibitor, CGS-16617, and a combination of both agents were evaluated for their ability to reduce the extension of myocardial infarct size in rats. Myocardial creatine kinase (CK) loss from the left ventricular free wall (LVFW) 48 hr after left coronary artery ligation was used as an index of ischemic damage. Treatment with either CGS-12970 (4 mg/kg) or CGS-16617 (1 microgram/kg) alone did not attenuate the loss of CK from LVFW significantly, compared with animals receiving only the vehicles for these drugs. However, the combined use of both agents significantly reduced CK depletion from LFVW (P less than 0.01). These findings support the interrelated role of TxA2 and angiotensin II as mediators of myocardial ischemia and suggest that combined inhibition of their formation may be useful in the treatment of acute myocardial infarction.
D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D003402:Creatine Kinase / Q000378:metabolism; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D011725:Pyridines; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; D003402:Creatine Kinase; D013930:Thromboxane-A Synthase; C052134:libenzapril