Abstract: TH-OR053

Bilateral Renal Cryo-Denervation Decreases Blood Pressure and Improves Insulin Sensitivity in Fructose-Fed Sprague Dawley Rats

Session Information

Category: Hypertension

  • 1101 Hypertension: Basic and Experimental - Neural and Inflammatory Mechanisms

Authors

  • Soncrant, Tyler, Wayne State University, Detroit, Michigan, United States
  • Beierwaltes, William H, Wayne State University, Detroit, Michigan, United States
  • Chen, Haiping, Wayne State University, Detroit, Michigan, United States
  • Wu, Min, Wayne State University, Detroit, Michigan, United States
  • Rossi, Noreen F., Wayne State University, Detroit, Michigan, United States
Background

Consumption of foods with fructose content is highly prevalent in modern diets with the average western intake at 17% of total calories. In combination with high salt intake, an elevated fructose diet leads to increased blood pressure and renal sympathetic nerve activity even prior to development of frank metabolic syndrome. Renal denervation reportedly improves glycemic control. We tested the hypothesis that bilateral cryo-denervation of the renal nerves will decrease mean arterial pressure (MAP) and improve insulin sensitivity in prediabetic fructose-fed rats on high salt diet.

Methods

Male Sprague Dawley rats were equipped with radiotransmitters to measure hemodynamics. They were given 20% fructose in their drinking water and 0.4% NaCl diet. After 7 days, they were either kept on 0.4% (LS) or switched to 4% NaCl (HS) diet for an additional 10-12 days. Control rats (C) were given plain water and 0.4% NaCl diet throughout. Rats were then subjected either to sham denervation (shamDNX) or bilateral denervation by alternately freezing (-150°C) and thawing the nerve 3 times (cryoDNX).

Results

One week later, MAP was unchanged in C or fructose-fed LS rats but had risen significantly in the fructose-fed HS rats from 110 ± 1 to 117± 2 mmHg; P< 0.05). Norepinephrine content decreased by 85% in cryoDNX vs shamDNX kidneys (P < 0.01). MAP did not change in shamDNX but returned to pre-diet levels cryoDNX fructose-fed HS rats (P < 0.05). Blood glucose (BG) was 100 ± 9 mg/dL in C rats vs 131 ± 8 mg/dL in conscious fructose-fed rats (P < 0.02). Glucose:insulin ratio in shamDNX rats was lower (47 ± 8) than in cryoDNX rats (105 ±18; P < 0.05) regardless of sodium intake, consistent with improved insulin sensitivity in the cryoDNX rats.

Conclusion

We conclude that bilateral renal denervation normalizes MAP in prediabetic fructose-fed rats on high salt diet and also improves insulin sensitivity in fructose-fed rats regardless of sodium intake. Further studies are needed to identify whether afferent inputs from or efferent sympathetic inputs to the kidney are involved. Thus, the renal nerves likely play important role in glucose disposal.

Funding

  • Veterans Affairs Support