Lymphocyte responses exacerbate angiotensin II-dependent hypertension

Steven D. Crowley, Young Soo Song, Eugene E. Lin, Robert Griffiths, Hyung Suk Kim, Phillip Ruiz

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Abstract

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-γ, interleukin-1β, and interleukin-6. By contrast, lymphocyte deficiency (i.e., scid mice) during ANG II infusion led to upregulation of tumor necrosis factor-α, 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 E2, 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 eNOSand COX-2-dependent pathways. inflammation; kidney diseases; T lymphocytes.

Original languageEnglish
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number4
DOIs
StatePublished - Apr 1 2010

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Angiotensin II
Lymphocytes
Hypertension
Kidney
Cyclooxygenase 2
Nitric Oxide Synthase Type III
Sodium
Angiotensins
Blood Pressure
Heart Injuries
Natriuresis
Kidney Diseases
Cardiomegaly
Epoprostenol
Interleukin-1
Dinoprostone
Interferons
Weight Loss
Immune System
Interleukin-6

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Lymphocyte responses exacerbate angiotensin II-dependent hypertension. / Crowley, Steven D.; Song, Young Soo; Lin, Eugene E.; Griffiths, Robert; Kim, Hyung Suk; Ruiz, Phillip.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 298, No. 4, 01.04.2010.

Research output: Contribution to journalArticle

Crowley, Steven D. ; Song, Young Soo ; Lin, Eugene E. ; Griffiths, Robert ; Kim, Hyung Suk ; Ruiz, Phillip. / Lymphocyte responses exacerbate angiotensin II-dependent hypertension. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2010 ; Vol. 298, No. 4.
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