title: Effect of an endothelin receptor antagonist and an angiotensin converting enzyme inhibitor on metabolism and contraction in the ischemic and reperfused rabbit heart.
abstract: The effect of an endothelin (ET) A/ETB receptor antagonist, TAK-044, and/or an angiotensin converting enzyme (ACE) inhibitor, temocaprilat, on myocardial metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After normothermic 15 min global ischemia, 60min of postischemic reperfusion was carried out. TAK-044 and/or temocaprilat was administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate, inorganic phosphate, pH, left ventricular systolic developed pressure (LVDev.P), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisted of seven hearts each: Group I consisted of controls, Group II was perfused with TAK-044 (10(-6) mol/L), Group III was perfused with temocaprilat (10(-6) mol/L), and Group IV was perfused with TAK-044 (10(-6) mol/L) in combination with temocaprilat (10(-6) mol/L). Group II showed a more early recovery of ATP during postischemic reperfusion (82+/-3%) compared with Group I (71+/-3%). Group III showed a significant inhibition of the decrease in ATP during global ischemia (54+/-3%) compared with Group I (45+/-3%). Group IV also showed a significant marked inhibition of the decrease in ATP during global ischemia (59+/-5%) and a more significant improvement on recovery of ATP during postischemic reperfusion (86+/-3%) compared with the other 3 groups. There were no differences in LVDev.P, LVEDP and coronary flow among these groups. In conclusion, TAK-044 in combination with temocaprilat had a significant potentiation on myocardial metabolism during both ischemia and reperfusion.
authors.affiliation: First Department of Internal Medicine, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kawabata
authors.forename: T
authors.initials: T
authors.lastname: Ryomoto
authors.forename: K
authors.initials: K
authors.lastname: Ishikawa
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D004734:Energy Metabolism / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010710:Phosphates / Q000032:analysis; D010725:Phosphocreatine / Q000032:analysis; D010759:Phosphorus Isotopes; D011817:Rabbits / Q000378:metabolism* / Q000502:physiology; D013841:Thiazepines / Q000494:pharmacology; D017725:Ventricular Pressure / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D010710:Phosphates; D010759:Phosphorus Isotopes; D013841:Thiazepines; D010725:Phosphocreatine; C088196:TAK 044; C069156:temocaprilat; D000255:Adenosine Triphosphate