The angiotensin II type 1 receptor mediates renal interstitial content of tumor necrosis factor-α in diabetic rats

Helmy M. Siragy, Alaa Awad, Peter Abadir, Randy Webb

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

A unique microdialysis technique was used to demonstrate that increased levels of angiotensin II (Ang II) and consequent stimulation of the Ang II type 1 (AT1) receptor increase the renal content of TNF-α in diabetes. Recovery of Ang II and TNF-α in renal interstitial fluid (RIF) was measured in conscious rats before and weekly for 12 wk after induction of diabetes with streptozocin and in response to oral valsartan (10 mg/kg·d). Recovery of Ang II in RIF was significantly higher in diabetic rats than in nondiabetic rats. In diabetic rats, RIF recovery of TNF-α increased by approximately 67% over baseline, whereas it was unchanged in nondiabetic rats. AT1 receptor blockade with valsartan prevented the increase in TNF-α in the diabetic group. This study shows that diabetes is associated with an increase in the vasoconstrictive hormone Ang II and the inflammatory cytokine TNF-α, both of which play a role in accelerating renal function decline in diabetic nephropathy. The study also confirms that valsartan reduces intrarenal level of TNF-α by acting on Ang II at the AT1 receptor level. This finding of a potential antiinflammatory effect for valsartan is new and in addition to its known antihypertensive effects.

Original languageEnglish (US)
Pages (from-to)2229-2233
Number of pages5
JournalEndocrinology
Volume144
Issue number6
DOIs
StatePublished - Jun 1 2003

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Valsartan
Angiotensin Type 1 Receptor
Angiotensin II
Tumor Necrosis Factor-alpha
Extracellular Fluid
Kidney
Experimental Diabetes Mellitus
Microdialysis
Diabetic Nephropathies
Antihypertensive Agents
Anti-Inflammatory Agents
Hormones
Cytokines

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Siragy, Helmy M. ; Awad, Alaa ; Abadir, Peter ; Webb, Randy. / The angiotensin II type 1 receptor mediates renal interstitial content of tumor necrosis factor-α in diabetic rats. In: Endocrinology. 2003 ; Vol. 144, No. 6. pp. 2229-2233.
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The angiotensin II type 1 receptor mediates renal interstitial content of tumor necrosis factor-α in diabetic rats. / Siragy, Helmy M.; Awad, Alaa; Abadir, Peter; Webb, Randy.

In: Endocrinology, Vol. 144, No. 6, 01.06.2003, p. 2229-2233.

Research output: Contribution to journalArticle

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