Abstract
Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.
Highlights
Renal denervation (RDN) is a novel therapy method for patients with resistant hypertension[8], heart failure[9], atrial fibrillation[10], ventricular tachyarrhythmias[11] and CKD12
The plasma level of B-type natriuretic peptide (BNP) was significantly decreased in renal denervation (RDN) group compared with Sham group (Fig. 1)
We firstly demonstrated that RDN has comprehensive anti-fibrosis effects on heart and kidneys
Summary
Renal denervation (RDN) is a novel therapy method for patients with resistant hypertension[8], heart failure[9], atrial fibrillation[10], ventricular tachyarrhythmias[11] and CKD12. These diseases were highly associated with organic fibrosis. We assumed that RDN could directly inhibit cardio-renal fibrosis through rebalancing RAAS (ACE/Ang II/AT1R & ACE2/Ang(1-7)/Mas-R) and decreasing SNS activity. In order to investigate the effects of RDN on cardio-renal fibrosis, we used a rat model of ISO-induced cardiomyopathy, which imitates chronic over-activity status of SNS and RAAS
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