Heart failure development in rats with ascending aortic constriction and angiotensin-converting enzyme inhibition.

Abstract

It remains unknown whether angiotensin-converting enzyme (ACE) inhibition can prevent heart failure in rats with a fixed high pressure load of the left ventricle and if this effect could be attributed to normalization of contractile protein phenotype and cardiac collagen content. Rats with constriction of the ascending aorta were treated with the ACE inhibitor quinapril (6 mg kg(-1) day(-1)) (n=95) or placebo (n=96) (starting 6 weeks post surgery. Quinapril treatment improved survival markedly (P<0.0000001) during the 24 weeks observation period. There were 69 deaths with placebo and only 25 deaths with quinapril. At the end of the observation period signs of left ventricular backward failure were, however, detected in 75 rats with placebo and in 67 rats treated with quinapril (P=0.229). Cox proportional hazard model with time-dependent covariates was used to document that the effect of quinapril treatment had been dependent on time. Quinapril had no significant effect on the development of morphological signs of left ventricular dysfunction after the first 54 days of treatment. The increased isomysin V(3) proportion of hypertrophied non-failing hearts was also not affected by quinapril treatment. Irrespective of treatment, failing hypertrophied hearts were characterized by an increase in left ventricular volume (P<0.05), percentage of the 'foetal' isomyosin V(3) (P<0.05), and hydroxyproline concentration (P<0.05). While the cause of the improved survival remains unknown, quinapril did apparently not interfere with the restitution of 'foetal' gene expression of pressure overloaded cardiomyocytes leading to depressed myocardial performance, ventricular dysfunction and the consecutive myocardial fibrosis.

• Authors: M Turcani, H Rupp
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 130 Issue 7 Pg. 1671-7 (Aug 2000) ISSN: 0007-1188 [Print] England
• PMID: 10928973 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Isoquinolines
• Tetrahydroisoquinolines
• Collagen
• Peptidyl-Dipeptidase A
• Quinapril
• Hydroxyproline

Topics

• Analysis of Variance
• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Animals
• Aorta (enzymology, physiopathology)
• Cardiac Output, Low (physiopathology)
• Collagen (metabolism)
• Disease Models, Animal
• Hydroxyproline (metabolism)
• Isoquinolines (pharmacology, therapeutic use)
• Male
• Peptidyl-Dipeptidase A (drug effects, metabolism)
• Quinapril
• Rats
• Rats, Wistar
• Tetrahydroisoquinolines
• Treatment Outcome
• Vasoconstriction (drug effects)