Effect of Ac-SDKP on Cardiac and Renal Collagen Deposition in Aldosterone-Salt Hypertension
Ac-SDKP is a natural substrate for the N-terminal active site of ACE. We have data showing that Ac-SDKP inhibits collagen synthesis both in vitro and in vivo. In the present study, we tested whether Ac-SDKP prevents cardiac and renal fibrosis in a renin-independent model of hypertension (aldosterone-salt) characterized by renal and cardiac fibrosis. Uninephrectomized adult SD rats were divided into 3 groups: control (saline) and aldosterone-salt (18 μg/d) alone or combined with Ac-SDKP 800 μg/kg/d.Saline, aldosterone or Ac-SDKP was given s.c.via osmotic pump for 6 weeks. We found that Ac-SDKP decreased collagen content (hydroxyproline assay) in the LV, right ventricle (RV) and kidney, and LV collagen fraction, with no significant effect on BP and LV hypertrophy (Table). Our results suggest that Ac-SDKP prevents cardiac and renal fibrosis in renin-independent hypertension. This indicates that Ac-SDKP could participate in the antifibrotic effect of ACEi, since ACEi inhibit fibrosis in this model of hypertension and markedly increase plasma Ac-SDKP.