Changes in Hsp60 level of the failing heart following acute myocardial infarction and the effect of long-term treatment with trandolapril.

Abstract

Changes in heat shock protein (Hsp) 60 of the viable left ventricular muscle (viable LV) after myocardial infarction in rats and the effect of the angiotensin I-converting enzyme inhibitor (ACEI) trandolapril were examined. Myocardial infarction was induced in rats by ligation of the left coronary artery. The coronary artery-ligated (CAL) and sham-operated (Sham) rats were orally treated with 3 mg/kg/d trandolapril from the 2nd to 8th week after surgery. Hemodynamic parameters and tissue weights of the left and right ventricles of the animals at the 8th week after CAL (8w-CAL rats) showed signs indicating chronic heart failure. An increase in Hsp60 content, a decrease in mitochondrial oxygen consumption rate (OCR), and an increase in the mitochondrial thiobarbiturate-reacting substance (TRS) of the viable LV were detected. Eight weeks after CAL. Long-term treatment of the CAL rats with trandolapril improved the hemodynamic parameters, attenuated the CAL-induced increase in Hsp60 content, the decrease in mitochondrial OCR, and the increase in the mitochondrial TRS content of the viable LV at the 8th week after myocardial infarction. The increase in Hsp60 content was closely related to the decrease in the mitochondrial OCR and to a rise in the LVEDP of the CAL animal at the 8th week after myocardial infarction. These results suggest that a series of pathophysiological alterations, including a reduction in mitochondrial function, appearance of reactive oxygen stress, and production of Hsp60 is involved in the development of cardiac failure and that trandolapril is beneficial for preventing these alterations.

• Authors: Wakako Toga, Kouichi Tanonaka, Satoshi Takeo
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 30 Issue 1 Pg. 105-10 (Jan 2007) ISSN: 0918-6158 [Print] Japan
• PMID: 17202668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Chaperonin 60
• Indoles
• Thiobarbituric Acid Reactive Substances
• trandolapril

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Animals
• Antihypertensive Agents (pharmacology, therapeutic use)
• Blood Pressure (drug effects)
• Chaperonin 60 (metabolism)
• Chronic Disease
• Disease Models, Animal
• Heart (drug effects, physiopathology)
• Heart Failure (etiology, metabolism, physiopathology, prevention & control)
• Heart Rate (drug effects)
• Indoles (pharmacology, therapeutic use)
• Male
• Mitochondria, Heart (drug effects, metabolism)
• Myocardial Infarction (complications, drug therapy, metabolism, physiopathology)
• Myocardium (metabolism, pathology)
• Oxidative Stress (drug effects)
• Oxygen Consumption (drug effects)
• Rats
• Rats, Wistar
• Thiobarbituric Acid Reactive Substances (metabolism)
• Time Factors
• Ventricular Function, Left (drug effects)
• Ventricular Remodeling (drug effects)