IL-10 treatment decreases blood pressure in male, but not female, spontaneously hypertensive rats
Ellen E. Gillis, Jacqueline B. Musall, Babak Baban, Jennifer C. Sullivan
Abstract
Interleukin-10 (IL-10) is an anti-inflammatory cytokine that induces nitric oxide (NO) production. IL-10 supplementation has been previously shown to lower blood pressure (BP) in male hypertensive mice, but the effect of exogenous IL-10 in hypertensive female rodents has not been studied. For the present study, we hypothesized that chronic infusion of IL-10 in hypertensive rats would lower BP concomitant with an increase in renal NO synthase (NOS) activity. Male and female spontaneously hypertensive rats (SHRs; 12 wk old) were randomized to receive IL-10 infusion by subcutaneous minipump (3.5 µg·kg −1 ·day −1 ) or serve as sham controls ( n = 4–6 rats per treatment per sex). BP was measured by tail cuff before and after 2 wk of treatment. Renal T cells and IL-10 were measured by flow cytometry, and NOS activity was determined by conversion of radiolabeled arginine to radiolabeled citrulline. Female SHRs had greater IL-10 + renal cells than male SHRs and greater expression of the IL-10 receptor at baseline. BP did not change in female SHRs treated with IL-10, but BP significantly decreased following IL-10 infusion in male SHRs. Contrary to our hypothesis, NOS enzymatic activity decreased with IL-10 treatment in the renal inner medulla and cortex of both sexes. Renal regulatory T cells also decreased in both sexes after IL-10 treatment. In conclusion, despite male SHRs having less IL-10 and IL-10 receptor expression in the kidney compared with female SHRs, exogenous IL-10 selectively decreased BP only in male SHRs. Furthermore, our data suggest that exogenous IL-10-induced decreases in BP in male SHRs are not dependent on upregulating renal NOS activity.