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Abstract: TH-PO856

Microangiography Reveals the Protective Role of Liraglutide on Renal Microvascular Impairment in Rats with Metabolic Syndrome

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Sukumaran, Vijayakumar, National Cerebral and Cardiovascular Centre, Suita, Osaka, Japan
  • Tsuchimochi, Hirotsugu, National Cerebral and Cardiovascular Centre, Suita, Osaka, Japan
  • Sonobe, Takashi, National Cerebral and Cardiovascular Centre, Suita, Osaka, Japan
  • Shirai, Mikiyasu, National Cerebral and Cardiovascular Center, Suita, Japan
  • Pearson, James T., National Cerebral and Cardiovascular Centre, Suita, Osaka, Japan
Background

Progressive renal impairment associated with metabolic syndrome remains a significant cause of morbidity and mortality. We investigated whether chronic high dose liraglutide (LIRA, GLP-1 agonist) treatment affects the metabolic profile and extent of renal inflammation and renal endothelial function in lean fa/+ and obese fa/fa (ZFDM) rats.

Methods

8-week old lean fa/+ and obese fa/fa ZFDM rats were treated with vehicle or LIRA (1mg/kg/day, subcutaneous) for 8 weeks. Systolic blood pressure (SBP) was monitored in ZFDM rats at 0, 4 and 8 weeks using tail-cuff method. Glomerular filtration rate (GFR) was measured in conscious rats at 0, 4 and 8 weeks using the fluorescein isothiocyanate sinistrin method. X-ray microangiography was then used to investigate renal vascular function (vessels 70-350 µm diameter). Further, renal function parameters including urinary albumin, creatinine and albumin creatinine ratio were measured.

Results

We found that in comparison to the saline treated obese fa/fa rats, LIRA treated rats had significantly lower SBP, and restored GFR (Fig. 1A-B) due in part to an increase in nitric oxide-mediated vasodilation in small renal arteries and arterioles (<200 µm diameter) (Fig. 1C-F). Further, vessel internal diameter, visible vessel number and caliber (%) increased after LIRA treatment compared to vehicle-treated rats (Fig. 1G-I). Moreover, the high dose LIRA treatment largely prevented the decline in renal function seen in vehicle treated obese fa/fa rats (elevated urinary albumin and depressed creatinine).

Conclusion

These results strongly suggest that high dose LIRA treatment significantly improved the endothelial function of microvessels in the renal circulation, and greatly improved renal function.