N‐Acetyl‐Seryl‐Aspartyl‐Lysyl‐Proline (Ac‐SDKP) Delays the Development of Hypertension and Renal Damage in Systemic Lupus Erythematosus (SLE)

SLE is an autoimmune disease with high prevalence of hypertension. Ac‐SDKP is naturally occurring peptide with anti‐inflammatory and immunomodulatory properties. In classical hypertension models, Ac‐SDKP prevents renal damage without affecting systolic blood pressure (SBP). We hypothesize that in autoimmune systemic diseases associated with hypertension, such as SLE, in addition to preventing renal damage, Ac‐SDKP also prevents the development of hypertension. Here we used NZBWF1 mice as SLE hypertension model. Female NZW (control) or NZBWF1 (SLE) mice were divided in 4 groups: 1) control+vehicle, 2) control+Ac‐SDKP, 3) SLE+vehicle, 4) SLE+Ac‐SDKP. Animals were treated with vehicle or Ac‐SDKP (800 µg/kg/d via minipumps) from 25 to 38 wks of age. Urine albumin and SBP were recorded weekly. Plasma anti‐dsDNA antibodies were measured at 38wks. At 28 wks of age 40 % of the animals in the SLE+vehicle group developed albuminuria (defined as urine albumin 蠅 30 µg/24hs), while in the SLE+Ac‐SDKP group the incidence of albuminuria was 10 %. At 32 wks of age the incidence of hypertension (defined as SBP 蠅 140 mmHg) in SLE+vehicle was 40 %, while none of the animals in SLE+Ac‐SDKP group developed hypertension. At 32 wks, the survival rate was 60 % in SLE+vehicle group and 90% in SLE+Ac‐SDKP 90 % group. However, at 38 wks of age the incidence of albuminuria, hypertension, mortality and plasma dsDNA antibody levels were similar between SLE+vehicle and SLE+Ac‐SDKP groups. In SLE, Ac‐SDKP delays the incidence of renal damage, hypertension and mortality without affecting the dsDNA antibody levels. Supported by NIH HL028982 and AHA 13PRE17100074