Progression of Kidney Injury and Cardiac Remodeling in Obese Spontaneously Hypertensive Rats: The Role of Renal Sympathetic Innervation

• Published in: American journal of hypertension 2015-02, Vol.28 (2), p.256-265
• Main Authors: Linz, Dominik, Hohl, Mathias, Schütze, Jonathan, Mahfoud, Felix, Speer, Thimoteus, Linz, Benedikt, Hübschle, Thomas, Juretschke, Hans-Paul, Dechend, Ralf, Geisel, Jürgen, Rütten, Hartmut, Böhm, Michael
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - metabolism; Animals; Blood Pressure; Creatinine - metabolism; Disease Progression; Hypertension - complications; Hypertension - physiopathology; Kidney - innervation; Kidney - physiopathology; Magnetic Resonance Imaging; Male; Myocardium - pathology; Obesity - complications; Obesity - physiopathology; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Renal Insufficiency, Chronic - etiology; Renal Insufficiency, Chronic - metabolism; Sympathectomy; Sympathetic Nervous System; Ventricular Remodeling
• ISSN: 0895-7061; 1941-7225
• DOI: 10.1093/ajh/hpu123

BACKGROUND Hypertension and metabolic syndrome (MetS) are associated with increased sympathetic activation possibly contributing to the progression of renal damage and cardiac remodeling. Renal sympathetic denervation (RDN) decreases sympathetic renal efferent and afferent nerve activity. METHODS Obese spontaneously hypertensive rats (SHRs-ob) were subjected to RDN at the age of 34 weeks (SHRs-ob + RDN) and were compared with sham-operated SHRs-ob and their normotensive lean controls (Ctrs). Blood pressure was measured by telemetry. Kidney and heart function were determined by magnetic resonance imaging (MRI). Renal and cardiac remodeling were characterized by immunohistochemical analyses. Animals were killed at the age of 48 weeks. RESULTS In SHRs-ob, RDN attenuated the progressive increase in blood pressure and preserved a mean blood pressure of 156±7mm Hg compared with 220±8mm Hg in sham-operated SHRs-ob at 100 days after RDN, whereas heart rate, body weight, and metabolic parameters remained unchanged. Renal catecholamine and tyrosine hydroxylase levels were significantly reduced after RDN, suggesting effective renal denervation. Progression of renal dysfunction as characterized by increased urinary albumin/creatinine ratio and reduced glomerular filtration rate were attenuated by RDN. In SHRs-ob, renal perfusion was significantly reduced and normalized by RDN. Cardiac fibrosis and cardiac diastolic dysfunction measured by MRI and invasive pressure measurements were significantly attenuated by RDN. CONCLUSIONS In SHRs-ob, progressive increase in blood pressure and progression of renal injury and cardiac remodelling are mediated by renal sympathetic activation as they were attenuated by RDN.