CHBPR N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Attenuates Renal Injury and Dysfunction in Hypertensive Rats with Reduced Renal Mass

摘要

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring peptide whose plasma concentration is increased 4- to 5-fold by angiotensin-converting enzyme inhibitors. We previously reported that in models of both hypertension and postmyocardial infarction, Ac-SDKP reduces cardiac inflammation and fibrosis. However, it is unknown whether Ac-SDKP can prevent or reverse renal injury and dysfunction in hypertension. In the present study, we tested the hypothesis that in rats with 5/6 Nephrectomy (5/6Nx) -induced hypertension, Ac-SDKP reduces renal damage, albuminuria and dysfunction by decreasing inflammatory cell infiltration and renal fibrosis and increasing nephrin protein. Ac-SDKP (800 μg/kg/day, i.p. via osmotic mini-pump) or vehicle was either a) started 7 days before 5/6Nx (prevention) and continued for 3 weeks or b) started 3 weeks after 5/6Nx (reversal) and continued for up to 6 weeks. Rats with 5/6Nx developed high blood pressure (BP), left ventricular hypertrophy (LVH), albuminuria, decreased glomerular filtration rate (GFR) and increased macrophage infiltration (inflammation) and renal collagen content (fibrosis). Ac-SDKP did not affect BP or LVH in either group; however, it significantly reduced albuminuria, renal inflammation and fibrosis and improved GFR in both prevention and reversal groups. Moreover, slit diaphragm nephrin protein expression in the glomerular filtration barrier was significantly decreased in hypertensive rats. This effect was partially prevented or reversed by Ac-SDKP. We concluded that Ac-SDKP greatly attenuates albuminuria and renal fibrosis and improves renal function in rats with 5/6Nx. These effects may be related to decreased inflammation (macrophages) and increased nephrin protein.