Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy.

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.

• Authors: Qian Liu, Qi Zhang, Kai Wang, Shengchan Wang, Dasheng Lu, Zhenzhen Li, Jie Geng, Ping Fang, Ying Wang, Qijun Shan
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 18582 (Dec 22 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26689945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• Inflammation Mediators
• Peptide Fragments
• Procollagen
• procollagen Type III-N-terminal peptide
• Angiotensin II
• Natriuretic Peptide, Brain
• Isoproterenol

Topics

• Angiotensin II (blood)
• Animals
• Biomarkers (blood)
• Cardiomyopathies (blood, chemically induced, complications, diagnostic imaging)
• Cytokines (blood)
• Denervation
• Fibrosis
• Heart Atria (pathology)
• Heart Ventricles (pathology)
• Inflammation Mediators (metabolism)
• Isoproterenol
• Kidney (innervation, pathology)
• Kidney Diseases (blood, complications, pathology)
• Male
• Myocardium (pathology)
• Natriuretic Peptide, Brain
• Peptide Fragments (blood)
• Procollagen (blood)
• Rats, Sprague-Dawley
• Renin-Angiotensin System