Improvement in baroreflex control of renal sympathetic nerve activity in obese Sprague Dawley rats following immunosuppression.

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.

Obesity depresses baroreflex control of renal sympathetic nerve activity and heart rate in Sprague Dawley rats: role of the renal innervation.

AIM: This study investigated the role of the renal innervation in arterial and cardiopulmonary baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) in rats fed a high-fat diet to induce obesity. METHODS: Rats received either a normal (12% kcal) or high (45% kcal) fat diet for 60 days. On day 61, rats were anesthetized and prepared for recording left RSNA. In one group, the renal nerves remained intact, while in the other, both kidneys were denervated. Baroreflex gain curves for RSNA and HR were generated by increasing and decreasing blood pressure. Low-pressure baroreceptors were challenged by infusing a saline load. RESULTS: Mean blood pressure was 135 mmHg in the fat-fed and 105 mmHg (P < 0.05) in normal rats. Weight gain, adiposity index and creatinine clearance were 37, 82 and 55% higher (P < 0.05-0.001), but urine flow rate and fractional sodium excretions were 53 and 65% (both P < 0.001) lower, respectively, in the fat-fed compared to normal rats. In fat-fed rats with innervated kidneys, RSNA and HR arterial baroreflex sensitivities were reduced by 73 and 72% (both P < 0.05) but were normal in renally denervated rats. Volume expansion decreased RSNA by 66% (P < 0.001) in normal rats, but not in the intact fat-fed rats and by 51% (P < 0.01) in renally denervated fat-fed rats. CONCLUSION: Feeding a high-fat diet caused hypertension associated with dysregulation of the arterial and cardiopulmonary baroreflexes which was dependent on an intact renal innervation. This suggests that in obese states neural signals arising from the kidney contribute to a deranged autonomic control.