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Effect of angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor antagonist on metabolism and contraction in ischemia-reperfused rabbit heart.

Abstract
The effect of angiotensin converting enzyme (ACE) inhibitor, temocaprilat and/or angiotensin II type 1 (AT1) receptor antagonist, CV-11974 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, postischemic reperfusion of 60min was carried out. Temocaprilat and/or CV-11974 were administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular developed pressure (LVDevP), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: group I consisted of controls, group II was perfused with temocaprilat (10(-6)mol/L), group III was perfused with CV-11974 (10(-6)mol/L), and group IV was perfused with temocaprilat (10(-6)mol/L) in combination with CV-11974 (10(-6) mol/L). Groups II and III showed a significant (p<0.05) inhibition of an overshoot phenomenon of PCr during postischemic reperfusion compared with group I. Group IV also showed a more pronounced significant (p<0.01) inhibition of the overshoot of PCr during reperfusion compared with group I. Groups II, III and IV showed a significant (p<0.05) inhibition of the decrease in ATP during global ischemia (59+/-2, 54+/-3 and 54+/-7%, respectively) compared with group I (45+/-3%). Groups II and IV showed a significant (p<0.05) early recovery of ATP during reperfusion (81+/-2, 80+/-6%) compared with group I (71+/-3%) and group II (73+/-2%). Group IV showed no more significant recovery in ATP than group III. There were no differences in LVDevP, LVEDP and coronary flow among these groups. In conclusion, temocaprilat in combination with CV-11974 has significant potential for improving myocardial energy metabolism during both myocardial ischemia and reperfusion.
AuthorsH Kawabata, T Ryomoto, K Ishikawa
JournalJapanese circulation journal (Jpn Circ J) Vol. 64 Issue 4 Pg. 276-82 (Apr 2000) ISSN: 0047-1828 [Print] Japan
PMID10783050 (Publication Type: Journal Article)
Chemical References
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • Thiazepines
  • temocaprilat
  • candesartan
Topics
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
  • Animals
  • Antihypertensive Agents (pharmacology, therapeutic use)
  • Benzimidazoles (pharmacology, therapeutic use)
  • Biphenyl Compounds
  • Child
  • Humans
  • Myocardial Contraction (drug effects)
  • Myocardial Ischemia (drug therapy, physiopathology)
  • Myocardial Reperfusion Injury (drug therapy, physiopathology)
  • Rabbits
  • Tetrazoles (pharmacology, therapeutic use)
  • Thiazepines (pharmacology, therapeutic use)

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