Female SHR have greater blood pressure sensitivity and renal T cell infiltration following chronic NOS inhibition than males

作者：Krystal N. Brinson, Ahmed A. Elmarakby, Ashlee J. Tipton, G. Ryan Crislip, Tatsuo Yamamoto, Babak Baban, Jennifer C. Sullivan · 发表于：American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · 年份：2013 · DOI：10.1152/ajpregu.00226.2013 · 被引用次数：40 · 研究领域：Nitric Oxide and Endothelin Effects、Renin-Angiotensin System Studies、Neuroendocrine regulation and behavior

Nitric oxide is a critical regulator of blood pressure (BP) and inflammation, and female spontaneously hypertensive rats (SHR) have higher renal nitric oxide bioavailability than males. We hypothesize that female SHR will have a greater rise in BP and renal T cell infiltration in response to nitric oxide synthase (NOS) inhibition than males. Both male and female SHR displayed a dose-dependent increase in BP to the nonspecific NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME: 2, 5, and 7 mg·kg(-1)·day(-1) for 4 days each); however, females exhibited a greater increase in BP than males. Treatment of male and female SHR with 7 mg·kg(-1)·day(-1) L-NAME for 2 wk significantly increased BP in both sexes; however, prior exposure to L-NAME only increased BP sensitivity to chronic NOS inhibition in females. L-NAME-induced hypertension increased renal T cell infiltration and indices of renal injury in both sexes, yet female SHR exhibited greater increases in Th17 cells and greater decreases in regulatory T cells than males. Chronic L-NAME was also associated with larger increases in renal cortical adhesion molecule expression in female SHR. The use of triple therapy to block L-NAME-mediated increases in BP attenuated L-NAME-induced increases in renal T cell counts and normalized adhesion molecule expression in SHR, suggesting that L-NAME-induced increases in renal T cells were dependent on both increases in BP and NOS inhibition. Our data suggest that NOS is critical in the abi...