Myocardial β‐adrenergic reactivity in volume overload‐induced cardiac hypertrophy in the rat

Abstract

The purpose of this study was to evaluate the changes in myocardial beta-adrenergic reactivity in animals undergoing a 4 week cardiac volume overload. Aortocaval shunt (ACS) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoproterenol dose-effects (chronotropic, inotropic and lusitropic properties) were studied after 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 [125I]iodocyanopindolol, and the beta(1)/beta(2)-adrenoceptor ratio 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% increase 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 responses in heart rate, left ventricular systolic pressure, +dP/dtmax and -dP/dtmax responses following increasing doses of isoproterenol was observed, without change in the dose inducing maximum effect. Total beta-adrenoceptor characteristics and beta(1)/beta(2) ratio were unchanged. However, beta(1)-adrenoceptor density increased in epicardium while decreasing in endocardium of left ventricle from ACS rats. Rightward shift at lower doses of isoproterenol-induced cardiac responses in volume-overloaded rats are not likely due to overall beta-adrenoceptor density changes.

Characterization of cardiac hypertrophy and heart failure due to volume overload in the rat

“…We have demonstrated a progressive increase in cardiac mass; this is in agreement with the observations of others who have employed the same needle technique for creating the aortocaval shunt (6,7,8,11,22,40,41). It should be mentioned that there are several features unique to the cardiac hypertrophic growth induced by aortocaval shunt.…”

“…16,20,21,27,28). On the other hand, with the needle technique, the injury due to operation is minimized, and the shunt size can be controlled by using different sizes of needles (6,7,8,11,15,22,40,41). In this study, we have presented several novel findings, including the time course changes in myosin heavy chain isoform composition, enhanced responses to isoproterenol, increased ␤ 1 -AR density, and increased AC activity due to volume overload.…”

In vivo and in vitro cardiac responses to beta-adrenergic stimulation in volume-overload heart failure

“…Given that Iso potentiated myocyte fractional shortening in both sham and ACF mycoytes, and pilot studies showed that Iso elicited the same increase in p-Ser23/24 cTnI (PKA phosphorylation site), the in vivo responses are not likely accounted for only by a change in β 1 -AR protein. A similar conclusion was drawn a number of years ago by Communal et al [44]. It should also be recognized that isotonic contractions of cardiomyocytes do not always adequately reflect a working heart.…”

Effects of .BETA.-Blocker on Left Ventricular Remodeling in Rats with Volume Overload Cardiac Failure

“…Excessive activation of the sympathetic nervous system plays a major role in the development of detrimental LV remodeling and dilatation [1], and catecholamines reduce viability and protein synthesis in isolated adult cardiac myocytes [15]. However, Commual et al showed that there was no increase in the plasma concentrations of cathecholamines and a decrease in the ventricular cathecholamine level in the same AC shunt rats at 4 weeks post-surgery [7]. Wang et al demonstrated the unique characteristics of volume overloaded hearts in AC shunt rats: the β-receptor density (upregulation) and adenylyl cyclase activity increased significantly, even in the heart failure stage (16 weeks post-surgery) [21].…”