Attenuation of changes in G(i)-proteins and adenylyl cyclase in heart failure by an ACE inhibitor, imidapril.

Abstract

Cardiac dysfunction in animals with congestive heart failure due to myocardial infarction (MI) is known to be associated with a wide variety of defects in receptor and post-receptor mechanisms. Since the heart function have been shown to be improved by treatment with different angiotensin converting enzyme (ACE) inhibitors, we examined the effects of imidapril, an ACE inhibitor, on changes in post-receptor mechanisms involving adenylyl cyclase (AC) and G proteins in the failing heart. Heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated daily with 1 mg/kg (orally) imidapril for 5 weeks. The animals were assessed for their left ventricular function and crude membranes were isolated from the viable left ventricle and examined for AC activities as well as G-protein activities and expression. Animals with heart failure exhibited depressions in ventricular function and AC activities in the absence or presence of forskolin, NaF and Gpp(NH)p. The AC activity in the presence of pertussis toxin was increased whereas that in the presence of cholera toxin was decreased in the failing heart. Protein contents and mRNA levels for G(i)-proteins were increased whereas those for G(s)-proteins were unaltered in the infarcted heart. All these changes due to MI were prevented by imidapril treatment. The results indicate that the depressed cardiac function in the failing heart may partly be due to the direct effects of changes in AC and G(i) proteins.

• Authors: R Sethi, Q Shao, N Takeda, N S Dhalla
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) 2003 Jul-Sep Vol. 7 Issue 3 Pg. 277-86 ISSN: 1582-1838 [Print] England
• PMID: 14594552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Imidazoles
• Imidazolidines
• RNA, Messenger
• Cholera Toxin
• imidapril
• Pertussis Toxin
• GTP-Binding Protein alpha Subunits, Gi-Go
• Adenylyl Cyclases

Topics

• Adenylyl Cyclases (metabolism)
• Angiotensin-Converting Enzyme Inhibitors (metabolism)
• Animals
• Cholera Toxin (metabolism)
• GTP-Binding Protein alpha Subunits, Gi-Go (metabolism)
• Heart Failure (metabolism)
• Heart Ventricles (enzymology)
• Hemodynamics
• Imidazoles (metabolism)
• Imidazolidines
• Male
• Pertussis Toxin (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Second Messenger Systems (physiology)