{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:32:12Z","timestamp":1793151132631,"version":"4.5.0"},"reference-count":67,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p>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-\u03b3, interleukin-1\u03b2, and interleukin-6. By contrast, lymphocyte deficiency (i.e., scid mice) during ANG II infusion led to upregulation of tumor necrosis factor-\u03b1, 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<jats:sub>2<\/jats:sub>, 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.<\/jats:p>","DOI":"10.1152\/ajpregu.00373.2009","type":"journal-article","created":{"date-parts":[[2010,2,11]],"date-time":"2010-02-11T05:24:03Z","timestamp":1265865843000},"page":"R1089-R1097","source":"Crossref","is-referenced-by-count":220,"title":["Lymphocyte responses exacerbate angiotensin II-dependent hypertension"],"prefix":"10.1152","volume":"298","author":[{"given":"Steven D.","family":"Crowley","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University Medical Center and Durham Veterans Affairs Medical Center, Durham;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Soo","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University Medical Center and Durham 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