Superoxide anion curbs nitric oxide modulation of afferent arteriolar ANG II responsiveness in diabetes mellitus

Gwynn C. Schoonmaker, Rachel W. Fallet, Pamela K. Carmines

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Experiments were performed to test the hypothesis that the impact of endogenous nitric oxide (NO) on ANG II-induced renal arteriolar constriction is reduced in rats with insulin-dependent diabetes mellitus (65 mg/kg streptozotocin; STZ). Arteriolar diameter responses to exogenous ANG II were quantified before and during NO synthase inhibition (100 μM N(ω)-nitro-L- arginin; L-NNA) by using the in vitro blood-perfused juxtamedullary nephron technique. Afferent arteriolar lumen diameter averaged 20.7 ± 2.0 μm in Sham kidneys and 25.9 ± 1.3 μm in STZ kidneys (P < 0.05). Efferent arteriolar diameter did not differ between Sham and STZ rats. In kidneys from Sham rats, afferent and efferent arteriolar responses to ANG II (0.1- 10.0 nM) were exaggerated significantly by L-NNA. L-NNA also augmented efferent arteriolar ANG II responses in kidneys from STZ rats (high-glucose bath) but did not alter ANG II responses in afferent arterioles from STZ rats. L-NNA also accentuated efferent, but not afferent, arteriolar ANG II responses in STZ kidneys during acute restoration of bath glucose to normal levels. Superoxide dismutase (150 U/ml) restored the ability of L-NNA to allow exaggerated afferent arteriolar responses to ANG H in kidneys from STZ rats. These observations indicate that superoxide anion suppresses the modulatory influence of endogenous NO on ANG II-induced afferent arteriolar constriction in diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)F302-F309
JournalAmerican Journal of Physiology - Renal Physiology
Volume278
Issue number2 47-2
DOIs
StatePublished - Feb 2000

Keywords

  • Efferent arteriole
  • N(ω)-nitro-L-arginine
  • Rat
  • Streptozotocin
  • Superoxide dismutase

ASJC Scopus subject areas

  • Physiology

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