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Relations between myocardial contractility, myosin phenotype, and plasma angiotensin-converting enzyme activity in
F Lambert1, Y Lecarpentier, A M Lompré
1INSERM U275-Loa-Ensta-Ecole Polytechnique, Palaiseau, France.
Insights
Angiotensin-converting enzyme (ACE) inhibitors preserve heart function in cardiomyopathic Syrian hamsters by limiting changes in myosin heavy-chain (MHC) protein. Treatment did not alter twitch duration despite improvements in contractility.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Cardiomyopathy in Syrian hamsters (CSH) leads to reduced myocardial contractility.
- Angiotensin-converting enzyme (ACE) inhibitors are known to preserve cardiac function in CSH.
- The underlying mechanisms, particularly myosin heavy-chain (MHC) phenotype changes, require further investigation.
Purpose of the Study:
- To investigate the relationship between ACE inhibitor treatment, myosin isoform patterns, and mechanical properties in CSH.
- To determine if ACE inhibition preserves myocardial contractility by affecting MHC phenotype.
- To assess changes in Vmax and alpha-MHC content in response to perindopril treatment.
Main Methods:
- Left ventricular papillary muscles were isolated from CSH and control hamsters.
- Animals received either perindopril (PE) or placebo (PL) for 5 months.
- Myosin isoform patterns and mechanical properties (Vmax, twitch duration) were analyzed.
Main Results:
- Untreated CSH (PL) showed reduced Vmax and lower alpha-MHC compared to controls (C).
- Perindopril treatment (PE) in CSH resulted in higher Vmax and alpha-MHC compared to PL.
- A positive correlation was observed between Vmax and alpha-MHC in the overall population.
Conclusions:
- ACE inhibitor treatment in CSH is associated with preserved contractility and limited isomyosin shift.
- No direct cause-and-effect relationship between ACE inhibition and MHC shift was demonstrated.
- Adaptive changes in twitch duration were not observed in treated or untreated CSH.
Abstract:
Angiotensin-converting enzyme (ACE) inhibitors have been shown to preserve myocardial contractility in the cardiomyopathic Syrian hamster (CSH). To determine if this was related to changes in myosin heavy-chain (MHC) phenotype, myosin isoform patterns and mechanical properties were studied in the same left ventricular papillary muscle from CSH of the Bio 53.58-dilated strain. From age 1 to 6 months, 22 CSH randomly received either perindopril 1 mg/kg/day in distilled water (PE, n = 11) or distilled water only (PL, n = 11), and seven control golden Syrian hamsters (C) received distilled water by force-feeding. Compared to C, PL had a lower Vmax (p < 0.01), a lower amount of alpha-MHC (p < 0.01), and an unchanged twitch duration. In PE, as compared to PL, there was a higher Vmax (p < 0.05), a higher alpha-MHC (p < 0.05), and an unchanged twitch duration. There was a positive relationship between Vmax and alpha-MHC in the population taken as a whole (p < 0.01), and when muscles from C and PL groups were plotted together (p < 0.001), but neither within each group, nor when PL and PE were plotted together. Our study indicates that in CSH (a) the preserved contractility with ACE-inhibitor treatment is associated with limitation of isomyosin shift induced by the myopathic process, but no cause-to-effect relationship could be demonstrated on the basis of our data, and (b) adaptive changes in twitch duration were not observed either in untreated CSH or in perindopril-treated CSH, despite significant changes in alpha-MHC content.