Cardiovascular, Metabolic and Renal T‐cell Profile of Obese C57Bl6 mice: Role of Renal Nerves

Abstract

Hypertension (HTN) is a global epidemic and often occurs in concurrence with obesity and diabetes (i.e. metabolic syndrome). Recent clinical trials suggest that renal denervation (RDNX) decreases blood pressure (BP) and improves glucose metabolism in drug resistant hypertensive patients. Using a murine model we tested the hypothesis that obesity is associated with renal inflammation secondary to T cell infiltration, which activates renal sensory nerves and increases global sympathetic activity. 8‐week old C57Bl6 mice were fed either a low fat diet (LFD; 10 KCal% fat) or a high fat diet (HFD; 45 KCal% fat) for 10 weeks. Two parallel protocols were conducted. In a metabolic protocol, body weight, food intake, body composition and fasting blood glucose were measured. In a cardiovascular protocol, mice were implanted with radiotelemeters for measurement of BP. Mice on a HFD exhibited increased splenic T cells indicating peripheral inflammation, exhibited a metabolic syndrome phenotype including increased fat mass, HTN and hyperglycemia compared to LFD. RDNX but not Sham surgery after 12 weeks of HFD normalized BP (116 ± 4 in sham vs. 97 ± 6 mmHg in RDNX mice). RDNX had no effect on BP in LFD mice. Finally, RDNX had no effect on glucose metabolism as determined by glucose tolerance test. These results suggest that renal nerves play a role in obesity induced HTN but do not contribute to impaired glucose metabolism in this murine model. Future data analysis will test the hypothesis that renal inflammation drives renal afferent nerves and global sympathetic activity in obesity‐induced HTN. Supported by RO1HL116476.