Renal nitric oxide production is decreased in diabetics rats and improved by AT1 receptor blockade

Alaa S. Awad, Randy L. Webb, Robert M. Carey, Helmy M. Siragy

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Objective: Diabetes mellitus is associated with increased incidence of cardiovascular complications. Lack of nitric oxide production may exacerbate these complications. We hypothesized that diabetes decreases renal nitric oxide (NO) production, an effect that is reversed via inhibition of angiotensin subtype-1 receptor. Methods: We monitored changes in renal interstitial fluid nitric oxide by a microdialysis technique in the renal cortex of conscious Sprague-Dawley rats. Rats (n = 8 each group) were given streptozotocin 30 mg/kg intravenously to induce diabetes. Changes in renal interstitial fluid angiotensin II and NO were evaluated at baseline before and over 12 weeks during the development of diabetes and at 4 and 8 h after oral administration of the angiotensin subytype-1 (AT1) receptor blockers, losartan (30 mg/kg) or valsartan (10 mg/kg). Results: Renal interstitial fluid angiotensin II significantly increased after development of diabetes. In contrast, basal renal interstitial fluid nitric oxide decreased significantly over 12 weeks after development of diabetes. Both losartan and valsartan caused a further increase in renal angiotensin II levels. Some 4 h after administration, there was significantly greater increase in renal nitric oxide after administration of valsartan than of losartan. At 8 h post-treatment, only valsartan caused a significant increase in renal nitric oxide levels. Conclusion: These results demonstrate that diabetes mellitus is associated with an increase in renal production of angiotensin II, while renal production of nitric oxide is reduced. The decrease in renal NO is reversed by AT1 receptor blockade.

Original languageEnglish (US)
Pages (from-to)1571-1577
Number of pages7
JournalJournal of Hypertension
Volume22
Issue number8
DOIs
StatePublished - Aug 2004
Externally publishedYes

Keywords

  • Angiotensin II
  • Angiotensin subtype 1 receptor
  • Losartan
  • Nitric oxide
  • Valsartan

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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