Interaction of nitric oxide and transforming growth factor-β1 induced by angiotensin II and mechanical stretch in rat renal tubular epithelial cells

A. Miyajima, J. Chen, I. Kirman, D. P. Poppas, Jr Vaughan, D. Felsen

Research output: Contribution to journalArticle

49 Citations (Scopus)


Purpose: Changes in intrarenal pressure accompanying unilateral ureteral obstruction can result in tubular mechanical stretch and mediator release from renal tubules. Therefore, we examined the synthesis of nitric oxide and transforming growth factor-β (TGF-β), and their interaction in rat renal epithelial cells (NRK-52E) exposed to either angiotensin II or mechanical stretch. Materials and Methods: NRK-52E were exposed to either angiotensin II or mechanical stretch. Nitrite and TGF-β in the supernatant were assessed by the Greiss reaction and bioassay, respectively. The level of cell hypertrophy and intracellular TGF-β protein was determined by flow cytometry. TGF-β messenger RNA and inducible nitric oxide synthase protein were detected by reverse transcriptase polymerase chain reaction and Western blot, respectively. Results: Angiotensin II stimulated TGF-β1 and nitric oxide. The nitric oxide synthase inhibitor, N-nitro-L-arginine (L-NAME) or angiotensin II type I receptor blocker, losartan, inhibited nitric oxide and TGF-β1 induced by angiotensin II. Flow cytometry showed that either L-NAME or losartan inhibited angiotensin II induced cell hypertrophy. TGF-β1 inhibited iNOS protein and nitric oxide, whereas an anti-TGF-β antibody enhanced iNOS. Mechanical stretch induced TGF-β, inducible NOS protein and nitric oxide. However, TGF-β expression was not affected by L-arginine or L-NAME when cells were exposed to mechanical stretch. Conclusions: These results demonstrate that nitric oxide is an intermediate in angiotensin II stimulated TGF-β1 expression but not in stretch induced TGF-β expression, and that TGF-β1 is a negative regulator of nitric oxide in rat renal epithelial cells. The complex interaction of these cytokines may be a target for intervention in the fibrotic and apoptotic processes in the obstructed kidney.

Original languageEnglish
Pages (from-to)1729-1734
Number of pages6
JournalJournal of Urology
Issue number5
Publication statusPublished - 2000 Jan 1



  • Angiotensins
  • Nitric oxide
  • Transforming growth factor beta
  • Ureteral obstruction

ASJC Scopus subject areas

  • Urology

Cite this