Renoprotective Effects of N‐acetyl‐seryl‐aspartyl‐lysyl‐proline (Ac‐SDKP) in Dahl Salt‐Sensitive Rats

Abstract

Ac‐SDKP is a natural tetrapeptide, hydrolyzed by angiotensin‐converting enzyme, with anti‐inflammatory and anti‐fibrotic properties. The effect of Ac‐SDKP on Salt‐Sensitive (SS) hypertension is unknown; here, we hypothesized that Ac‐SDKP prevents renal inflammation, fibrosis, glomerulosclerosis and albuminuria in Dahl SS rats on high salt diet, without affecting the blood pressure. Dahl SS rats and their consomic controls, SS‐13BN were fed either 0.23% NaCl (low salt, LS) or 4% NaCl (high salt, HS) diet and infused with vehicle or Ac‐SDKP at either low or high dose (800 or 1600 µg/kg/day, respectively) subcutaneously via osmotic minipump for 6 weeks. Animals were divided into the following groups: LS + vehicle, HS + vehicle, HS + low AcSDKP, and HS + high AcSDKP.HS increased systolic blood pressure (SBP) in SS rats (HS + vehicle 186±5 vs. LS + vehicle 141±3 mmHg), but not in SS‐13BN rats (HS+vehicle 140±3 vs. LS+vehicle 140±2 mmHg). Ac‐SDKP did not affect SBP. In both strains, Ac‐SDKP prevented HS‐induced renal macrophage and T cell infiltration, interstitial fibrosis and glomeruloslerosis. In SS‐13BN rats, low dose of Ac‐SDKP were able to prevent albuminuria (marker of renal function) induced by HS (LS+vehicle 7±1 vs. HS + vehicle 44±8 vs. HS + low Ac‐SDKP 24±3.18 mg/24h), while in SS rats only high Ac‐SDKP dose had the same effect.In summary, at low and high doses, Ac‐SDKP prevented renal damages in SS rats on HS diet without affecting the blood pressure. But, only at high dose, Ac‐SDKP prevented HS‐induced albuminuria in this strain. On the other hand, in consomic controls, both doses of Ac‐SDKP prevented HS‐induced renal damages and albuminuria.Supported by NIH PPG grant P01HL028982