N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal injury and dysfunction in hypertensive rats with reduced renal mass: council for high blood pressure research.
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring peptide of which the plasma concentration is increased 4- to 5-fold by angiotensin-converting enzyme inhibitors. We reported previously 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 by increasing nephrin protein. Ac-SDKP (800 microg/kg per day, SC via osmotic minipump) or vehicle was either started 7 days before 5/6Nx (prevention) and continued for 3 weeks or started 3 weeks after 5/6Nx (reversal) and continued for another 3 weeks. Rats with 5/6Nx developed high blood pressure, left ventricular hypertrophy, albuminuria, decreased glomerular filtration rate, and increased macrophage infiltration (inflammation) and renal collagen content (fibrosis). Ac-SDKP did not affect blood pressure or left ventricular hypertrophy in either group; however, it significantly reduced albuminuria, renal inflammation, and fibrosis and improved glomerular filtration rate 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.
Liao
Tang-Dong
TD
Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Mich 48202-2689, USA.
Yang
Xiao-Ping
XP
D'Ambrosio
Martin
M
Zhang
Yanlu
Y
Rhaleb
Nour-Eddine
NE
Carretero
Oscar A
OA
D000419:Albuminuria / Q000188:drug therapy / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology / Q000517:prevention & control; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D009929:Organ Size; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D016482:Urinalysis
D009842:Oligopeptides; C410764:acetyl-seryl-aspartyl-(N-acetyl)-lysyl-proline