Effects of N-acetyl-seryl-asparyl-lysyl-proline on blood pressure, renal damage, and mortality in systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence of hypertension. NZBWF1 (SLE‐Hyp) mice develop hypertension that can be prevented by modulating T cells. The peptide N‐acetyl‐seryl‐aspartyl‐lysyl‐proline (Ac‐SDKP) decreases renal damage and improves renal function in a model of SLE without hypertension (MRL/lpr). However, it is not known whether Ac‐SDKP prevents hypertension in NZBWF1 mice. We hypothesized that in SLE‐Hyp, Ac‐SDKP prevents hypertension and renal damage by modulating T cells. Animals were divided into four groups: (1) control + vehicle, (2) control + Ac‐SDKP, (3) SLE + vehicle, and (4) SLE + Ac‐SDKP. Systolic blood pressure (SBP), albuminuria, renal fibrosis, and T‐cell phenotype were analyzed. SBP was higher in SLE compared to control mice and was not decreased by Ac‐SDKP treatment. Half of SLE mice developed an acute and severe form of hypertension accompanied by albuminuria followed by death. Ac‐SDKP delayed development of severe hypertension, albuminuria, and early mortality, but this delay did not reach statistical significance. Ac‐SDKP prevented glomerulosclerosis, but not interstitial fibrosis in SLE‐Hyp mice. SLE‐Hyp mice showed a decrease in helper and cytotoxic T cells as well as an increase in double negative lymphocytes and T helper 17 cells, but these cells were unaffected by Ac‐SDKP. In conclusion, Ac‐SDKP prevents kidney damage, without affecting blood pressure in an SLE animal model. However, during the acute relapse of SLE, Ac‐SDKP might also delay the manifestation of an acute and severe form of hypertension leading to early mortality. Ac‐SDKP is a potential tool to treat renal damage in SLE‐Hyp mice.