Abstract 322: Protective effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on renal damage in Dahl Salt-Sensitive Rats
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring tetrapeptide hydrolyzed by angiotensin-converting enzyme. We previously reported that Ac-SDKP protects the kidney from inflammation, fibrosis, and dysfunction caused by hypertension. Salt-sensitivity is highly prevalent in African-Americans and elderly patients, and is associated with a high rate of hypertensive renal disease.
The effect of Ac-SDKP on Salt-Sensitive (SS) hypertension is unknown; here, we hypothesized that Ac-SDKP prevents renal fibrosis, glomerulosclerosis and albuminuria in Dahl SS rats on high salt diet without affecting blood pressure.
Dahl SS rats and their consomic control, SS-13BN were fed either 0.23% NaCl (low salt, LS) or 4% NaCl (high salt, HS) diet and infused with Ac-SDKP (800 μg/kg/day, subcutaneously via osmotic minipump) or vehicle (0.01 N acetic acid) for 6 weeks. Animals were divided into following groups: LS+vehicle, HS+vehicle, and HS+Ac-SDKP.
High salt increased systolic blood pressure (SBP) in SS rats (HS+vehicle 186±5 vs. LS+vehicle 141±3 mmHg), but not in SS-13BN (HS+vehicle 140±3 vs. LS+vehicle 140±2 mmHg). Ac-SDKP did not affect SBP. In both SS and SS-13BN, HS induced renal and cardiac hypertrophy, which were not prevented by Ac-SDKP. However, in SS rats, Ac-SDKP prevented HS-induced renal interstitial fibrosis (HS+vehicle 12±0.5 vs. HS+Ac-SDKP 7±1 % of renal interstitial area) and glomeruloslerosis (HS+vehicle 18±1 vs. HS+Ac-SDKP 9±1 % of glomerular tuft area). Compared to LS, HS increased albuminuria in both strains, from 13±1 to 94±10 mg/24h in SS and from 7±1 to 44±8 mg/24h in SS-13BN. HS also decreased nephrin protein expression in both strains. Interestingly, in SS-13BN, Ac-SDKP attenuated albuminuria (24±3.18 mg/24h) and partially attenuated the decrease in nephrin expression, but in SS, Ac-SDKP had no effect on either albuminuria (126±34 mg/24h) or nephrin expression.
In summary, Ac-SDKP prevents renal fibrosis, glomerulosclerosis but not albuminuria in Dahl SS rats on high salt diet. On the other hand, the consomic controls fed high salt developed albuminuria and decreased nephrin, and these effects were prevented by Ac-SDKP.
Author Disclosures: M.E. Worou: None. M. D’Ambrosio: None. T. Liao: None. P. Nakagawa: None. N. Rhaleb: None. O.A. Carretero: None.
- © 2014 by American Heart Association, Inc.