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Rapid transient analysis of myosin cross-bridge kinetics in hypertrophied hearts
Insights
Antihypertensive therapy in spontaneously hypertensive rats (SHR) improved cardiac muscle function and reduced left ventricular hypertrophy. Treatment also prevented changes in myosin isoenzymes associated with pressure overload.
Area of Science:
- Cardiology
- Physiology
- Biochemistry
Background:
- Essential hypertension leads to left ventricular hypertrophy, increasing risks of coronary artery disease and heart failure.
- The spontaneously hypertensive rat (SHR) serves as a model to study long-term antihypertensive effects on myocardial contractility.
Purpose of the Study:
- To investigate mechanical and biochemical differences in papillary muscles of SHR and Wistar-Kyoto (WKY) rats.
- To assess the impact of age and antihypertensive treatment on these characteristics.
Main Methods:
- Comparison of papillary muscle mechanical properties (delayed force redevelopment) between SHR and WKY rats across different ages.
- Analysis of myosin isoenzyme patterns in treated and untreated SHR.
Main Results:
- SHR exhibited reduced delayed force redevelopment compared to WKY rats, evident even before hypertension onset.
- Antihypertensive treatment in SHR lowered blood pressure, reduced hypertrophy, and increased delayed force redevelopment.
- Treated SHR showed a shift in myosin isoenzymes towards V1 (fast) and away from V3 (slow) compared to untreated SHR.
Conclusions:
- Long-term antihypertensive therapy prevents left ventricular hypertrophy in SHR.
- Therapy may prevent hypertrophy by inhibiting the shift in myosin isoenzyme patterns typically seen under pressure overload.
Abstract:
Essential hypertension, with pressure overload leading to left ventricular hypertrophy, often results in coronary artery disease and congestive heart failure. The spontaneously hypertensive rat (SHR) is an attractive model for studying the effects of long-term antihypertensive therapy on the contractile properties of the myocardium. In this study we investigated differences in mechanical and biochemical characteristics of papillary muscles from SHR and normal (Wistar-Kyoto [WKY]) rats as a function of age and treatment. We found that the rate of delayed force redevelopment after rapid stretch was less in SHR than in WKY in every age group studied, even at 2 wk of age, before hypertension was evident in the SHR. In the treated SHR, blood pressure was lower, hypertrophy was reduced and the rate of delayed force redevelopment was increased compared with the untreated SHR. Finally, the pattern of myosin isoenzymes was different in treated than in untreated SHR, being shifted to more of the fast V1 and less of the slow V3 isomyosin. We conclude that long-term antihypertensive therapy not only prevents the development of left ventricular hypertrophy, but may do so by preventing the shift in myosin isoenzyme pattern normally found in hearts subjected to a long-term pressure overload.