Hypertensive Female Sprague Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal T regulatory cells.

We have previously shown that hypertensive female rats have more T regulatory cells (Tregs) which contribute more to blood pressure (BP) control in females vs males. Based on known protective properties of Tregs, the goal of this study was to investigate the mechanisms by which females maintain Tregs. The current study was designed to 1) compare the impact of three hypertension models on the percentage of renal Tregs and 2) test the hypothesis that NOS inhibition prevents increases in renal Tregs and exacerbates renal damage in female Sprague Dawley (SD) rats. Rats (11-14 weeks old) were randomized to one of 4 groups: control; norepinephrine (NE) infusion; angiotensin II (Ang II) infusion; or the NOS inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), in drinking water. BP was measured via tail-cuff. After 2 weeks of treatment, kidneys were isolated and processed to measure Tregs via flow cytometric analysis and renal injury via, urinary albumin excretion, plasma creatinine, and histological analyses. Hypertensive treatments increased BP in all experimental animals. Increases in BP in Ang II and NE treated rats were associated with increases in renal Tregs vs. control. In contrast, L-NAME treatment decreased Tregs compared to all groups. L-NAME treatment modestly increased albumin excretion. However, plasma creatinine was comparable among the groups and there was no histological evidence of glomerular or tubular injury. This study provides insight into the mechanisms regulating renal Tregs and supports that an intact NOS system is crucial for female rats to have BP-related increases in renal Tregs.