Myocardial Response to Stress in Cardiac Hypertrophy and Heart Failure: Effect of Antihypertensive Drugs^a

Abstract

The myocardium's response to increased stress or load is not stereotyped. Differences have been observed in the heart's molecular composition and performance characteristics when exposed to stress. Myosin isoforms gradually change during development of hypertrophy, whereas collagen levels change only during the chronic phase of hypertrophy. Cardiac hypertrophy can regress if treated with antihypertensive drugs, but the myocardium of the post-hypertrophic heart no longer has the same composition as it did before hypertrophy. In rat studies of the effects of antihypertensive drugs on cardiac functional reserve, captopril showed a regression of hypertrophy associated with a lower baseline stroke volume and, after dobutamine stress, a dose-dependent rise in stroke volume. In untreated rates captopril showed no change in stroke volume. In hydralazine-treated rats, there was no change in reserve after dobutamine stress, whereas propranolol treatment resulted in partial regression and a slight change in stroke volume. Overall, our data suggests that development of hypertension and hypertrophy plays a role in changes in the molecular structure of the myocardium, especially during the chronic phase of hypertrophy and heart failure. This complex process cannot be explained by one factor but involves a combination of factors. Identification of each factor would be of importance for the development of appropriate therapeutic agents.

Inhibition of NF-κB induces regression of cardiac hypertrophy, independent of blood pressure control, in spontaneously hypertensive rats

“…These results, therefore, indicate that captopril ameliorates cardiac hypertrophy in SHR and may indicate a possible involvement of NF-B. To elucidate further whether blood pressure may influence NF-B activation, we used hydralazine, a known vasodilator reported to normalize the blood pressure level but have no effects on cardiac mass (11,13,14,36). Our study showed that hydralazine normalized the blood pressure in SHR, as expected, but had no effect in either cardiac mass or NF-B activation.…”

“…It has been reported by numerous investigators (8,22,27,36) that captopril regresses cardiac hypertrophy and normalizes blood pressure, but this is the first report to show that captopril also inhibits NF-B activity as well. Recently, it has been reported that angiotensin II could activate NF-B in cardiac disease (4,30,38).…”

β-adrenergic blockade attenuates cardiac dysfunction and myofibrillar remodelling in congestive heart failure

“…A study in spontaneously hypertensive rats has shown that atenolol treatment reduced cardiac mass and affected the shift in MHC isozymes in the myocardium [46]. Likewise, we found that atenolol reduced ventricular hypertrophy, increased ␣-MHC and decreased ␤-MHC isoform in post-MI rats.…”

“…Thus some caution should be exercised while interpreting the observed changes in α‐MHC and β‐MHC in terms of quantitative alterations in myofibrillar protein content because we did not determine the absolute values for the MHC isozymes in the failing heart by employing mass spectroscopy [47], which is more accurate than the semi‐quantitative Coomassie staining. Although treatment of hypertensive animals with propranolol induced partial regression in cardiac hypertrophy, it did not improve stroke volume significantly [46]. On the other hand, treatment of infarcted animals with propranolol decreased RV hypertrophy and improved both echocardiographic and haemodynamic parameters.…”

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“…In any case, ACE inhibitor therapy administered to the failing SHR for a 2-4 month period, fails to reverse pathological features of the myocardium, improve papillary muscle function, or reduce myocardial fibrosis and stiffness. Sen [44] has pointed out that hypertrophy may regress with treatment but myocardium of the post-hypertrophic heart no longer has the same composition as it did prior to the development of hypertrophy; the same may be true for failure. Connective tissue remodeling of the heart is thought to contribute to impaired performance [10].…”