Faculty Collaboration Database

Renal protective effect of N-acetyl-seryl-aspartyl-lysyl-proline in dahl salt-sensitive rats. Hypertension 2015 Oct;66(4):816-22

Date

09/02/2015

Pubmed ID

26324505

Pubmed Central ID

PMC4658233

DOI

10.1161/HYPERTENSIONAHA.115.05970

Scopus ID

2-s2.0-84941207515 (requires institutional sign-in at Scopus site)   23 Citations

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.

Author List

Worou ME, Liao TD, D'Ambrosio M, Nakagawa P, Janic B, Peterson EL, Rhaleb NE, Carretero OA

Author

Pablo Nakagawa PhD Assistant Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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