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

Krystal N. Brinson, Ahmed A. Elmarakby, Ashlee J. Tipton, G. Ryan Crislip, Tatsuo Yamamoto, Babak Baban, Jennifer C. Sullivan

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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 NG-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-NAMEinduced increases in renal T cells were dependent on both increases in BP and NOS inhibition. Our data suggest that NOS is critical in the ability of SHR, females in particular, to maintain BP and limit a pro-inflammatory renal T cell profile.

Original languageEnglish (US)
Pages (from-to)R701-R710
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume305
Issue number7
DOIs
StatePublished - Oct 1 2013

Keywords

  • Hypertension
  • Inflammation
  • Kidney injury
  • Nitric oxide synthase
  • Sex

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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