REDUCTION BY ORAL PROPRANOLOL TREATMENT OF LEFT-VENTRICULAR HYPERTROPHY SECONDARY TO PRESSURE-OVERLOAD IN THE RAT

1 Studies on cardiac myocyte cell, cultures have postulated a role for alpha(1)-adrenoceptors and mechanical stretch in the induction of cel lular changes thought to be important in compensatory cardiac hypertro phy. However, in vivo work suggests that B-adrenoceptors are important and the present study was designed to analyse the effect of propranol ol on the cardiac hypertrophy caused by a pressure-overload in a way t hat takes account of the effects of propranolol on the work load itsel f. 2 The compensatory cardiac hypertrophy that develops in response to experimental coarctation of the aorta was studied in the rat. Pressur e gradients and total cardiac work load (expressed as rate x pressure product) were assessed, and the relationship between increasing cardia c work load and the resulting left ventricular hypertrophy was establi shed 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 coa rctation in the range of 15-31 mmHg, the animals on control diet showe d a 38% increase in left ventricular weight/body weight ratio (LV rati o) and a 30% increase in heart weight/body weight ratio (heart ratio), whereas rats given high dose oral propranolol-treatment showed increa ses of only 13% and 9%, respectively. 4 In a second series of rats wit h a wider range of pressure gradients, the regression lines of LV rati o 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 st eep in the propranolol-treated rats as in the controls. Thus, for the same increment in cardiac work load, the degree of compensatory cardia c hypertrophy in propranolol-treated rats was half that observed in co ntrols. 5 The reduction in compensatory cardiac hypertrophy was not as sociated with an increase in incidence of congestive heart failure and the propranolol-treated rats were able to sustain equally high (or hi gher) degrees of pressure over-load as controls did. 6 It is concluded that propranolol treatment approximately halves the compensatory card iac hypertrophy occurring in response to a left ventricular pressure o ver-load by a mechanism independent of its effect on cardiac work load . This finding provides further support for the view that noradrenalin e released from sympathetic nerve terminals in the heart exerts a trop hic effect on cardiac myocytes, and that the sympathetic nervous syste m may be the final common pathway in many forms of compensatory cardia c hypertrophy. In contrast to in vitro models, this effect appears to be largely mediated via beta-adrenoceptors in the intact animal.