Lymphocyte responses exacerbate angiotensin II-dependent hypertension.

Journal Article (Journal Article)

Activation of the immune system by ANG II contributes to the pathogenesis of hypertension, and pharmacological suppression of lymphocyte responses can ameliorate hypertensive end-organ damage. Therefore, to examine the mechanisms through which lymphocytes mediate blood pressure elevation, we studied ANG II-dependent hypertension in scid mice lacking lymphocyte responses and wild-type controls. Scid mice had a blunted hypertensive response to chronic ANG II infusion and accordingly developed less cardiac hypertrophy. Moreover, lymphocyte deficiency led to significant reductions in heart and kidney injury following 4 wk of angiotensin. The muted hypertensive response in the scid mice was associated with increased sodium excretion, urine volumes, and weight loss beginning on day 5 of angiotensin infusion. To explore the mechanisms underlying alterations in blood pressure and renal sodium handling, we measured gene expression for vasoactive mediators in the kidney after 4 wk of ANG II administration. Scid mice and controls had similar renal expression for interferon-gamma, interleukin-1beta, and interleukin-6. By contrast, lymphocyte deficiency (i.e., scid mice) during ANG II infusion led to upregulation of tumor necrosis factor-alpha, endothelial nitric oxide synthase (eNOS), and cyclooxygenase-2 (COX-2) in the kidney. In turn, this enhanced eNOS and COX-2 expression in the scid kidneys was associated with exaggerated renal generation of nitric oxide, prostaglandin E(2), and prostacyclin, all of which promote natriuresis. Thus, the absence of lymphocyte activity protects from hypertension by allowing blood pressure-induced sodium excretion, possibly via stimulation of eNOS- and COX-2-dependent pathways.

Full Text

Duke Authors

Cited Authors

  • Crowley, SD; Song, Y-S; Lin, EE; Griffiths, R; Kim, H-S; Ruiz, P

Published Date

  • April 2010

Published In

Volume / Issue

  • 298 / 4

Start / End Page

  • R1089 - R1097

PubMed ID

  • 20147609

Pubmed Central ID

  • PMC4422347

Electronic International Standard Serial Number (EISSN)

  • 1522-1490

Digital Object Identifier (DOI)

  • 10.1152/ajpregu.00373.2009


  • eng

Conference Location

  • United States