Renal protective effect of N-acetyl-seryl-aspartyl-lysyl-proline in dahl salt-sensitive rats

Authors

Morel E. Worou, Henry Ford Health
Tang-Dong Liao, Henry Ford HealthFollow
Martin D'Ambrosio
Pablo Nakagawa, Henry Ford Health
Brana Janic, Henry Ford HealthFollow
Edward L. Peterson, Henry Ford HealthFollow
Nour-Eddine Rhaleb, Henry Ford HealthFollow
Oscar A. Carretero, Henry Ford HealthFollow

Recommended Citation

Worou ME, Liao TD, D'Ambrosio M, Nakagawa P, Janic B, Peterson EL, Rhaleb NE, and Carretero OA. Renal protective effect of n-acetyl-seryl-aspartyl-lysyl-proline in dahl salt-sensitive rats. Hypertension. 2015;66(4):816-22.

Document Type

Article

Publication Date

10-1-2015

Publication Title

Hypertension

Abstract

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetrapeptide with anti-inflammatory and antifibrotic properties. Its effect on salt-sensitive (SS) hypertension is unknown. We hypothesized that in Dahl SS rats on high-salt (HS) diet, Ac-SDKP prevents loss of nephrin expression and renal immune cell infiltration, leading to a decrease in albuminuria, renal inflammation, fibrosis, and glomerulosclerosis. To test this, Dahl SS rats and consomic SS13BN controls were fed either a low-salt (0.23% NaCl) or HS (4% NaCl) diet and treated for 6 weeks with vehicle or Ac-SDKP at either low or high dose (800 or 1600 μg/kg per day, respectively). HS increased systolic blood pressure in SS rats (HS+vehicle, 186±5 versus low salt+vehicle, 141±3 mm Hg; P<0.005) but not in SS13BN rats. Ac-SDKP did not affect blood pressure. Compared with low salt, HS-induced albuminuria, renal inflammation, fibrosis, and glomerulosclerosis in both strains, but the damages were higher in SS than in SS13BN. Interestingly, in SS13BN rats, Ac-SDKP prevented albuminuria induced by HS (HS+vehicle, 44±8 versus HS+low Ac-SDKP, 24±3 or HS+high Ac-SDKP, 8±1 mg/24 h; P<0.05), whereas in SS rats, only high Ac-SDKP dose significantly attenuated albuminuria (HS+vehicle, 94±10 versus HS+high Ac-SDKP, 57±7 mg/24 h; P<0.05). In both strains, Ac-SDKP prevented HS-induced inflammation, interstitial fibrosis, and glomerulosclerosis. In summary, in SS rats on HS diet, at low and high doses, Ac-SDKP prevented renal damage without affecting the blood pressure. Only the high dose of Ac-SDKP attenuated HS-induced albuminuria. Conversely, in SS13BN rats, both doses of Ac-SDKP prevented HS-induced renal damage and albuminuria.

Medical Subject Headings

Animals; Blood Pressure; Disease Models, Animal; Glomerular Filtration Rate; Growth Inhibitors; Hypertension; Kidney; Male; Oligopeptides; Rats; Rats, Inbred Dahl

PubMed ID

26324505

Volume

66

Issue

4

First Page

816

Last Page

822