Improvement in baroreflex control of renal sympathetic nerve activity in obese Sprague Dawley rats following immunosuppression
S. A. Khan; M. Z. A. Sattar; N. A. Abdullah; H. A. Rathore; A. Ahmad; M. H. Abdulla; E. J. Johns
Year of publication
Acta Physiol (Oxf)
AIM: This investigation explored the hypothesis that in obesity an inflammatory response in the kidney contributed to a renal nerve-dependent blunting of the baroreflex regulation of renal sympathetic nerve activity. METHODS: Rats received a normal (12% kcal) or high-fat (45% kcal) diet for 8 weeks plus daily injections of vehicle (0.9% NaCl i.p) or tacrolimus (0.25 mg kg(-1) day(-1) i.p) from weeks 3-8. Following anaesthesia, left renal sympathetic nerve activity was recorded, baroreflex gain curves were generated, by infusing phenylephrine and sodium nitroprusside, and cardiopulmonary baroreceptors challenged by infusing a saline load. RESULTS: The high-fat diet elevated weight gain and adiposity index by 89 and 129% (both, P < 0.001). Mean blood pressure (132 ± 4 vs 103 ± 5 mmHg), fractional noradrenaline excretion and creatinine clearance (5.64 ± 0.55 vs 3.32 ± 0.35 mL min(-1) kg(-1) ) were 28, 77 and 69% higher (all P < 0.05), but urine flow and fractional sodium excretions were 42 and 72% (both P < 0.001) lower compared to normal rats. Plasma and renal TNF-α and IL-6 concentrations were fourfold to fivefold (P < 0.001) and 22 and 20% higher (both, P < 0.05), in obese rats but normalized following tacrolimus. In obese rats, baroreflex sensitivity was reduced by 80% (P < 0.05) but restored by renal denervation or tacrolimus. Volume expansion reduced renal sympathetic nerve activity by 54% (P < 0.001) in normal and obese rats subjected to renal denervation and tacrolimus, but not in obese rats with an intact renal innervation. CONCLUSION: Obesity induced a renal inflammation and pointed to this being both the origin of autonomic dysregulation and a potential focus for targeted therapy.