MYOCARDIAL BETA-ADRENERGIC REACTIVITY IN VOLUME OVERLOAD-INDUCED CARDIAC-HYPERTROPHY IN THE RAT

The purpose of this study was to evaluate the changes in myocardial be ta-adrenergic reactivity in animals undergoing a 4 week cardiac volume overload. Aortocaval shunt (ACS) or sham operation (sham) were perfor med in male Wistar rats, and 4 weeks later, isoproterenol dose-effects (chronotropic, inotropic and lusitropic properties) were studied afte r pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index were evaluated in plasma and heart ventricles, while beta-adrenoceptor characteristics in ventricle homogenates and slices with [I-125]iodocyanopindolol, and the beta(1)/beta(2)-adrenoceptor ra tio were estimated. Four weeks of cardiac volume overload resulted in a 55% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 3.9 +/- 0.1 mg/g in sham and ACS rats, respectively) and a 20% inc rease in protein contents (from 11.3 +/- 0.7 to 13.8 +/- 1.1 mg/100 mg ventricles in sham and ACS rats, respectively). Furthermore, NA and A concentrations and NA turn-over index were increased in ACS rats (14, 40 and 80% versus sham, respectively). A shift to the right of the re sponses in heart rate, left ventricular systolic pressure, +dP/dt(max) and -dP/dt(max) responses following increasing doses of isoproterenol was observed, without change in the dose inducing maximum effect. Tot al beta-adrenoceptor characteristics and beta(1)/beta(2) ratio were un changed. However, beta(1)-adrenoceptor density increased in epicardium while decreasing in endocardium of left ventricle from ACS rats. Righ tward shift at lower doses of isoproterenol-induced cardiac responses in volume-overloaded rats are not likely due to overall beta-adrenocep tor density changes. (C) 1998 Elsevier, Paris.