Myocardial β‐adrenergic reactivity in pressure 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 pressure-overload. Abdominal aortic constriction (AAC) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoprenaline dose-effects (chronotropic, inotropic and lusitropic properties) were studied after pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index (DHPG /NE ratio) were evaluated in 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 pressure overload resulted in a 70% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 4.2 +/- 0.3 mg/g in sham and AAC rats, respectively) and a 24% increase in protein contents (from 11.3 +/- 0.7 to 14.0 +/- 1.1 mg/100 mg ventricle in sham and AAC rats respectively). The ventricle NA content was similar in AAC and sham, while the ventricle A content and NA turn-over index were significantly increased in AAC rats (35 and 80% vs sham, respectively). Dose response of isoprenaline was significantly shifted to the right for all studied effects in AAC rats. However, maximal response (in relative values) was similar in AAC and sham rats only for heart rate but not for parameters depending on left ventricle contractile response. The beta-adrenoceptor density was significantly decreased in AAC by 30% without apparent affinity change and due to decreases in beta (1)-sites in septum and to beta (1)- and beta (2)-adrenoceptors in left ventricle endocardium. Decreases in isoprenaline-induced cardiac responses in AAC rats are associated with beta (1)-adrenoceptor density reduction and modification of beta (1)- and beta (2)-adrenoceptor ratio. These modifications are not the only reason for such dose response changes, at least for contractile response.

Prevention of Heart Failure in Rats by Trimetazidine Treatment: A Consequence of Accelerated Phospholipid Turnover?

“…In heart failure resulting from myocardial infarction in rat, the down-regulation is mainly due to a selective ␤ 1 -AR decrease without change in K d (Rutger et al, 2000). In cardiac hypertrophy due to abdominal ascending aortic banding, the ␤ 1 -AR downregulation occurs together with a reduced ␤ 1 /␤ 2 ratio (Communal et al, 1998). In this study, as expected, we observed a significant decrease in ␤ 1 -AR density, which paralleled the rise in plasma BNP and thus the severity of heart failure.…”

DEFECTIVE INTRACELLULAR Ca2+ HOMEOSTASIS CONTRIBUTES TO MYOCYTE DYSFUNCTION DURING VENTRICULAR REMODELLING INDUCED BY CHRONIC VOLUME OVERLOAD IN RATS

“…Conversely, reports from others 25,39 suggest an attenuated response of volume overload‐induced failing hearts to β‐adrenoceptor stimulation. Downregulation of β‐adrenoceptor stimulation was also reported in failing hearts induced by pressure overload 44 and myocardial infarction 45 . Downregulation of β‐adrenoceptor stimulation in failing hearts following chronic volume overload was attributed to reduced β 1 ‐adrenoceptor density, diminished adenylyl cyclase activity and decreased expression of G sα ‐proteins 46,47 .…”

β-Adrenergic signaling in rat heart is similarly affected by continuous and intermittent normobaric hypoxia

“…It is known that the total number of myocardial β-ARs is closely related to catecholamine levels but a selective decrease in β 1 -ARs has usually been observed during cardiac hypertrophy. The vast majority of studies focused on this issue were done in the LV (Galinier et al 1992;Communal et al 1998;Sethi et al 2007). For RV hypertrophy, a significant decrease in the total number of β-ARs was also reported but receptor subtypes were not discriminated in these early studies (Ishikawa et al 1991;Yoshie et al 1994;Mardon et al 1998).…”