Zheng H, Liu X, Sharma NM, Patel KP. Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of -adrenoceptors. Am J Physiol Heart Circ Physiol 311: H337-H346, 2016. First published June 10, 2016; doi:10.1152/ajpheart.00999.2015.-Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area Ͼ30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) Ͼ20 mmHg.  1-and 2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of  1-adrenoceptor (by 47%) and 2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 g/kg)-induced increase in ϩdP/dt (by 71%) and ϪdP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts -adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. renal nerve; sympathetic nerve activity; cardiac function; heart failure
NEW & NOTEWORTHYThis study shows in a comprehensive way that renal denervation initiated after a period of chronic heart failure enhances cardiac contractility and the responsiveness of hearts to isoproterenol stimulation, and these effects are due in part to renal denervation-induced increase in -adrenoceptor protein and function.WORLDWIDE, MORE THAN 100 MILLION people are afflicted with chronic heart failure (HF), imposing a significant burden on the health care systems throughout the world. Chronic overactivation of the sympathetic nervous system is one of the major pathophysiological soliloquy abnormalities leading to the progression of chronic HF (28,29,48). Activation of sympathetic outflow is initially a hemodynamic adaptation to compensate for decreased cardiac function and output. This adaptation also includes an increase in Na ϩ and fluid retention and activation of the renin-angiotensin-aldosterone system (11, 34). Additional adverse effects of elevated sympathetic drive directed toward the heart have been shown to result in the desensitization or downreg...