Renoprotective effect of dulaglutide in L-NAME-induced hypertensive nephropathy in rats: insight into the roles of PPAR-gamma and VEGF.

Hypertensive nephropathy (HTNeph), primarily triggered by vascular endothelial dysfunction, is the second most common cause of end-stage renal disease. This study investigates the ameliorative effect of dulaglutide, a glucagon-like peptide-1 receptor agonist, on HTNeph via its impact on renal vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptors-gamma (PPARγ). The effect of dulaglutide (0.2 mg/kg/day, s.c.) for six weeks on L-NAME-induced hypertension (50 mg/kg/day, i.p.) was investigated in rats. Renal function biomarkers, serum IL-10 and TNF-α, tissue redox balance, histopathological and immunohistochemical changes, and PPARγ gene expression were assessed. Coadministration of dulaglutide with L-NAME could recover renal glomerular and vascular histological structure, reduce collagen deposition, increase the anti-inflammatory IL-10 and the reno-protective PPARγ level, elevate the immunohistochemical expression of the renal tubular eNOS and VEGF, and substantially reduce TNF-α activity in hypertensive rats. Our research linked dulaglutide's anti-inflammatory, antifibrotic, antioxidant, and vascular endothelium-promoting qualities to its capacity to upregulate VEGF and PPARγ, which confer its reno-protective effects. Thus, dulaglutide is presented as a potential candidate to shield patients from HTNeph. Dulaglutide ameliorates hypertensive nephropathy in rats via preserving renal function's biomarkers, restoring tissue redox balance, increasing the anti-inflammatory marker IL-10 and decreasing the inflammatory marker TNF-α, elevating the renoprotective PPARγ gene expression, amending renal vasculopathy and glomerular injury, decreasing fibrosis, and increasing the immunohistochemical expression of eNOS and VEGF.