Abstract
Metabolic syndrome is a common risk factor for chronic kidney disease. We investigated whether liraglutide (LIRA, glucagon like peptide (GLP)-1 receptor agonist) treatment improved renal vascular function and renal remodeling in male Zucker rats on a high-salt diet (6% NaCl). 8-week old Zucker lean (+/+) and Zucker obese (fa/fa) rats were treated with vehicle or LIRA (0.1mg/kg/day) for 8 weeks on high-salt diet. Glomerular filtration rate (GFR) was measured at 0 and 8 weeks using FITC-sinistrin method in conscious rats. We used X-ray microangiography to measure renal arterial vessel diameter (70-350µm) and vessel number in vivo in anesthetized rats. Renal protein expression levels of NT, CD-68, eNOS, VEGF, TGF-β1, COX-2 and GLP-1R were assessed by Western blotting. Renal gene expressions were determined by real time-PCR. In contrast to vehicle-treated, fa/fa-LIRA rats improved GFR, nitric oxide (NO)-mediated vasodilation in response to ACh and SNP in small arterial vessels (<200 µm diameter). LIRA treatment increased vessel responsivity to NO donors in comparison to vehicle treatment. Increases in the expressions of proinflammatory, profibrotic and oxidative stress related genes in fa/fa rats relative to +/+ were unaltered by LIRA, other than a trend for attenuation of VCAM-1 gene expression. However, LIRA treatment increased protein expressions of eNOS (p=0.014) and VEGF (p=0.063), while reducing glomerular macrophage infiltration in comparison to vehicle-treated fa/fa rats. Low-dose LIRA treatment improved renal vascular function through amelioration of vascular dysfunction and improved NO-mediated dilation of small intrarenal arteries and arterioles, and a reduction in renal inflammation.
- The American Society for Pharmacology and Experimental Therapeutics