EXPERIMENTAL AND MOLECULAR PATHOLOGY 41, 390-396 (1984) Adrenergic Activity as a Modulating Factor in the Genesis of Myocardial Hypertrophy in the Rat ARTURO GENOVESE, MASSIMO CHIARIELLO, MARIANO BOZZAOTRE. SALVATORE LATTE, WALTER DE ALFIERI,AND MARIO CONDORELLI Department of Medicine, II School qf Medicine. University of Naples. Naples. Italy Recei\,ed April 6. 1984. und in revised form July 6. 1984 Sprague Dawley male rats (200-220 g) were subjected to a long-term treatment with low doses of catecholamines in an attempt to assess the effect of the adrenergic stimulation on ventricular weights, hemodynamics. and hydroxyproline content in the myocardium. Data are presented indicating that both exogenous catecholamines (i.e.. isoproterenol) and en- dogenous catecholamines (released from tyramine) are able to bring about a degree of myocardial hypertrophy associated with a significant increase in the ventricular concentra- tions of hydroxyproline, without affecting hemodynamic parameters (blood pressures and heart rate). Thus the modulation of sympathetic tone in the genesis of cardiac hypertrophy is demonstrated, and a direct effect of the catecholamines on cardiac cells is postulated which is independent of hemodynamic changes. cc I984 Academic Pres. Inc. INTRODUCTION In previous papers we claimed that rats exposed to chronic pressure overload of the right ventricle in a hypobaric chamber developed a significant degree of bilateral ventricular hypertrophy (Genovese et al.. 1982, 1983). The left ventric- ular enlargement in the absence of systemic overload is in line with a number of clinical and experimental studies suggesting a complex situation rather than a direct relationship between pressure load and cardiac hypertrophy. Extensively the pathophysiology of the left-right heart interrelationship in many cardiac dis- eases has long been investigated and remains to be clearly defined. It is of interest to mention the results of the Shimane Heart Study showing left ventricular hy- pertrophy in early hypertensive children (Nishio et al., 1978). Other studies report the hypertrophic response of the left ventricle in normotensive patients with chronic obstructive pulmonary disease and elevated pulmonary pressure (Rao et nf., 1968; Baum e? al., 1971). Finally several reviews of autopsies on adult men with car pulmonale showed that in the majority of cases of right ventricular hypertrophy a left ventricular hypertrophy was associated (Scott and Garvin, 1941; Spatt and Grayzel, 1948; Michelson, 1960; Murphy el al., 1974). In several experimental models in the rat the contralateral ventricle which was not exposed to pressure overload showed a significant degree of hypertrophy (Buccino et al., 1969; Cutilletta et al., 1978; Frohlich and Tarazi, 1979). In par- ticular attention was focused on the influence of the adrenergic drive in the genesis of cardiac hypertrophy. Thus catecholamines were suggested to play an important role in modulating the development of ventricular hypertrophy (Sen et al., 1974; Weiss et al., 1974; Yamori et al., 1979). The aim of this study is to explore further the role of adrenergic stimulation on the development of myocardial hypertrophy. Thus the changes in dry weight of the left ventricle, right ventricle, and interventricular septum were studied in rats following the long-term administration of selective doses of isoproterenol 390 0014-4800184 $3.00 Copyright 0 1984 by Academic Preaa. Inc. All ngbts of reproduction in any form reserved.