Bilatel Ranal Denervation Ameliorates Isoproterenol-induced Heart Failure

Chronic heart failure(CHF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system(RAS) activity and elevated levels of proinflammatory cytokines(PICs). Renal denervation(RD) has been shown to restore autonomic balance and to improve cardiac function in CHF[1], but the protective mechanisms remain unclear. This study was to observe the changes of isoproterenol(isoprenaline) induced cardiac function and central mechanism by rena denervtion and further observe the expression of RAS and PICs level in the brain.This study was completely randomized ctrolled trial deign. Under the pre-test results, we calculate the sample size of this experiment n = 40. the experimental animals were randomly divided into four groups, the sham + saline group(sham + saline); renal denervation + saline group(RD + saline); sham + isoproterenol group(sham + iSO); renal denervation + isoproterenol group(RD + iSO). Conscious male rats undergoing RD were instrumented with telemetric probes to observe hemodynamic and autonomic changes during ISO infusion. Discovering the components of RAAS and PICs involved in cardiovascular regulation in the heart and brain By RT-PCR. Effects of RD on cardiac dysfunction and mRNA expression of the RAS and PICs were also determined after ISO infusion. ISO resulted in a remarked decrease in blood pressure(BP) and a significant increase in heart rate(HR), which was accompanied by decreased baroreflex sensitivity(spontaneous) and HR variability and by increased BP variability. Notably, these autonomic changes were reversed by RD. By the end of ISO infusion, rats exhibited cardiac dysfunction and hypertrophy along with reduced baroreflex sensitivity(pharmacological). RD significantly improved cardiac dysfunctions and baroreflex sensitivity and attenuated myocardial hypertrophy. RT-PCR analysis revealed that ISO upregulated mRNA expression of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulation. RD reversed the expression of these genes. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced CHF, and that downregulated RAS and PICs in the brain contribute to these cardiac benefits of RD.