title: Effects of an HMG-CoA reductase inhibitor in combination with an ACE inhibitor or angiotensin II type 1 receptor antagonist on myocardial metabolism in ischemic rabbit hearts.
abstract: We investigated the effects of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, an angiotensin converting enzyme (ACE) inhibitor, temocaprilat, and an angiotensin II type 1 (AT1) receptor antagonist, CV-11974, on myocardial metabolism during ischemia in isolated rabbit hearts using phosphorus 31-nuclear magnetic resonance (31P-NMR) imaging. Forty-five minutes of continuous normothermic global ischemia was carried out. Pravastatin, temocaprilat, CV-11974 or a nitric oxide synthase inhibitor, L-NAME was administered from 60 min prior to the global ischemia. Japanese white rabbits were divided into the following experimental groups, a control group (n=7), a group treated with pravastatin (P group; n=7), a group treated with pravastatin and temocaprilat (P+T group; n=7), a group treated with pravastatin and CV-11974 (P+CV group; n=7), and a group treated with pravastatin and L-NAME (P+L-NAME group; n=7). During ischemia, P group, as well as either P+T group or P+CV group, showed a significant inhibition of the decreases in adenosine triphosphate (ATP) and intracellular pH (pHi) (p<0.01, respectively, at the end of ischemia compared to the control group as well as P+L-NAME group), and a significant inhibition of the increase in inorganic phosphate (Pi) (p<0.01, respectively, compared with the control group as well as P+L-NAME group). These results suggest that pravastatin significantly improved myocardial energy metabolism during myocardial ischemia. This beneficial effect was dependent on NO synthase. However, this beneficial effect was not enhanced by either temocaprilat or CV-11974.
authors.affiliation: First Department of Internal Medicine, Kinki University School of Medicine, Osakasayama, Japan. int1@med.kindai.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kawabata
authors.forename: Kizuku
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Kinji
authors.initials: K
authors.lastname: Ishikawa
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002316:Cardiotonic Agents / Q000494:pharmacology; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002316:Cardiotonic Agents; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010710:Phosphates; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D013841:Thiazepines; C069156:temocaprilat; D000255:Adenosine Triphosphate; D017035:Pravastatin; C081643:candesartan; D019331:NG-Nitroarginine Methyl Ester