Abstract
1. Studies on cardiac myocyte cell cultures have postulated a role for alpha 1-adrenoceptors and mechanical stretch in the induction of cellular changes thought to be important in compensatory cardiac hypertrophy. However, in vivo work suggests that beta-adrenoceptors are important and the present study was designed to analyse the effect of propranolol on the cardiac hypertrophy caused by a pressure-overload in a way that takes account of the effects of propranolol on the work load itself. 2. The compensatory cardiac hypertrophy that develops in response to experimental coarctation of the aorta was studied in the rat. Pressure gradients and total cardiac work load (expressed as rate x pressure product) were assessed, and the relationship between increasing cardiac work load and the resulting left ventricular hypertrophy was established in a control group and compared with left ventricular hypertrophy in a group treated with a high dose of oral propranolol (80 mg kg-1 body weight). 3. In the rats with mean pressure gradients over the coarctation in the range of 15-31 mmHg, the animals on control diet showed a 38% increase in left ventricular weight/body weight ratio (LV ratio) and a 30% increase in heart weight/body weight ratio (heart ratio), whereas rats given high dose oral propranolol-treatment showed increases of only 13% and 9%, respectively. 4. In a second series of rats with a wider range of pressure gradients, the regression lines of LV ratio versus mean pressure gradient, and of LV ratio versus cardiac work, were different in the two groups with a slope that was only half as steep in the propranolol-treated rats as in the controls. Thus, for the same increment in cardiac work load, the degree of compensatory cardiac hypertrophy in propranolol-treated rats was half that observed in controls. 5. The reduction in compensatory cardiac hypertrophy was not associated with an increase in incidence of congestive heart failure and the propranolol-treated rats were able to sustain equally high (or higher) degrees of pressure over-load as controls did. 6. It is concluded that propranolol treatment approximately halves the compensatory cardiac hypertrophy occurring in response to a left ventricular pressure over-load by a mechanism independent of its effect on cardiac work load. This finding provides further support for the view that noradrenaline released from sympathetic nerve terminals in the heart exerts a trophic effect on cardiac myocytes, and that the sympathetic nervous system may be the final common pathway in many forms of compensatory cardiac hypertrophy. In contrast to in vitro models, this effect appears to be largely mediated via beta-adrenoceptors in the intact animal.
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Selected References
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