Renin-angiotensin system and sympathetic nervous system in cardiac pressure-overload hypertrophy

Abstract

Angiotensin II and norepinephrine (NE) have been implicated in the neurohumoral response to pressure overload and the development of left ventricular hypertrophy. The purpose of this study was to determine the temporal sequence for activation of the renin-angiotensin and sympathetic nervous systems in the rat after 3-60 days of pressure overload induced by aortic constriction. Initially on pressure overload, there was transient activation of the systemic renin-angiotensin system coinciding with the appearance of left ventricular hypertrophy (day 3). At day 10, there was a marked increase in AT(1) receptor density in the left ventricle, increased plasma NE concentration, and elevated cardiac epinephrine content. Moreover, the inotropic response to isoproterenol was reduced in the isolated, perfused heart at 10 days of pressure overload. The affinity of the beta(2)-adrenergic receptor in the left ventricle was decreased at 60 days. Despite these alterations, there was no decline in resting left ventricular function, beta-adrenergic receptor density, or the relative distribution of beta(1)- and beta(2)-receptor sites in the left ventricle over 60 days of pressure overload. Thus activation of the renin-angiotensin system is an early response to pressure overload and may contribute to the initial development of cardiac hypertrophy and sympathetic activation in the compensated heart.

Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway

“…Although the adrenergic receptor blockers are widely used to prevent cardiac hypertrophy (25,26), the underlying mechanisms of their effect remain to be elucidated. It has also been reported that sympathetic activation plays a critical role in the pressure-overload rat model of abdominal aortic constriction (27,28). In this regard, adrenergic receptor blockade is likely to be an effective tool for the prevention of pressure overload-induced ventricular hypertrophy.…”

Role of myofibrillogenesis regulator-1 in myocardial hypertrophy

“…One of these is induction of AAS in rats, which leads to systemic hypertension, LV hypertrophy, and activation of the reninangiotensin-aldosterone system (1,3). Using a model of AASinduced cardiac hypertrophy, we assessed cardiac function, blood pressure, and LV hypertrophy in adult Sprague-Dawley rats.…”

Enhanced vascular contractility and diminished coronary artery flow in rats made hypertensive from diet-induced obesity

“…25 After general anesthesia with intraperitoneal pentobarbital (60 mg/kg) and heparin (1500 U/kg), the heart from each rat was quickly extracted from the thoracic cavity, immersed in ice-cold Krebs buffer, and mounted onto a nonrecirculating heart-perfusion apparatus. Retrograde perfusion through the aorta was initiated with oxygenated Krebs buffer (in mmol/l: NaCl 128, potassium chloride (KCl) 4.8, KH 2 PO4 1.2, MgSO 4 1.2, NaHCO 3 25, dextrose 11, CaCl 2 1.6; EDTA 2 pmol/l; PaO 2 500-600 mm Hg; pH 7.4) and maintained at a constant temperature of 371C.…”