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

## TL;DR

Dulaglutide helps protect rat kidneys from hypertension damage by reducing inflammation and improving blood vessel health.

## Contribution

This study shows dulaglutide's reno-protective effects in hypertensive nephropathy via upregulation of VEGF and PPARγ.

## Key findings

- Dulaglutide reduces renal fibrosis and improves glomerular and vascular structure in hypertensive rats.
- The drug increases anti-inflammatory IL-10 and PPARγ while decreasing pro-inflammatory TNF-α.
- Dulaglutide elevates eNOS and VEGF expression, promoting vascular endothelium health.

## Abstract

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

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

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.