Abstract 12006: Renal Sympathetic Denervation Improves Both Progressive Cardiac Remodeling and Renal Damages in Hypertensive Heart Failure Rats: Comparison With β Receptor Blockade

Abstract

Background: Chronic activation of sympathetic-nervous system (SNS) is triggered and contributes to subsequent cardiac remodeling and the transition to heart failure (HF). Hypothesis: Renal sympathetic denervation (RDN) may affect the process by improving the renal damage and suppressing cardiac SNS in rat hypertensive HF model with renal injury. The effects may be comparable to those of chronic β blocker treatment. Methods and Results: In Dahl salt-sensitive hypertensive rats, RDN or sham operation was performed at hypertrophic stage (11 weeks). Vehicle (CONT) or β blocker, bisoprolol (BISO) was administrated in rats with sham operation. Both RDN and BISO did not alter blood pressure during the study, but BISO group showed the significantly less heart rate. In RDN and BISO groups, the median survival time was significantly improved from 18.9 (CONT) to 21.4 and 22.5 weeks, respectively (P < 0.01). Echocardiography showed the improvement of LV dilatation and fractional shortening, and histological analysis showed the amelioration of myocyte hypertrophy and fibrosis in RDN and BISO groups at HF stage (17 weeks). β1 adrenergic receptor and tyrosine hydroxylase expression in LV myocardium was significantly increased only in RDN group. In contrast, α1b, α1d, and α2c adrenergic receptor expressions were improved only in BISO group. Furthermore, renal histopathologic damages and function were ameliorated in the both treatment groups. It was accompanied by suppression of local endothelin-1 and renin mRNA expressions. Conclusions: Renal sympathetic denervation ameliorated progression of both myocardial and renal damages in the hypertensive rats, independent of blood pressure. The overall effects were similar with those of chronic β receptor blockade having the effects on heart rate and α adrenergic receptors’ expression. The underlying mechanism may be associated with preservation of myocardial sympathetic-nervous system and renal protection.