High glucose augments angiotensin II action by inhibiting NO synthesis in in vitro microperfused rabbit afferent arterioles

Shuji Arima, Sadayoshi Ito, Ken Omata, Kazuhisa Takeuchi, Keishi Abe

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33 Citations (Scopus)


Preglomerular afferent arteriole (Af-Art) is a crucial vascular segment in the control of glomerular hemodynamics. We have recently reported that vascular reactivity of Af-Art is modulated by nitric oxide (NO). However, little is known about its reactivity under pathophysiological conditions such as diabetes, which is often accompanied by abnormal glomerular hemodynamics. In the present study, we examined the direct effects of high glucose, the hallmark of diabetes, on the vascular reactivity of Af-Art. Rabbit Af-Arts were microperfused for three hours with medium 199 containing either normal (5.5 mM; NG-Af-Arts) or high concentrations (30 mM; WG30-Af-Arts) of glucose, and then vascular reactivity was examined. Sensitivity to angiotensin II (Ang II) was significantly higher in HG30-Af-Arts than in NG-Af-Arts. Ang II began to cause significant constriction from 10-9 M in NG-Af-Arts (18 ± 3%, N = 6, P < 0.01) and from 10-9 M in HG30-Af-Arts (9 ± 2%, N = 6, P < 0.01). NO synthesis inhibition with 10-4 M nitro-L-arginine methyl ester (L-NAME) increased the sensitivity to Ang II in NG-Af-Arts without affecting Ang II action in HG30-Af-Arts. In L-NAME-pretreated NG-Af-Arts, Ang II began to cause constriction from 10-11 M (11 ± 3%, N = 6, P < 0.01). Thus, pretreatment with L-NAME abolished the difference in sensitivity to Ang II between NG- and HG30-Af-Arts, suggesting impaired NO synthesis in HG30-Af-Arts. Indeed, 10-5 M of acetylcholine, which cause vasodilation through NO, dilated preconstricted NG-Af-Arts by 79 ± 12% (N = 6) but only by 16 ± 4% (N = 7) in HG30-Af-Arts. These results suggest that abnormal glomerular hemodynamics which accompany diabetes are due, at least in part, to the impaired modulatory role of NO in the Vascular reactivity of Af-Art.

Original languageEnglish
Pages (from-to)683-689
Number of pages7
JournalKidney international
Issue number3
Publication statusPublished - 1995 Sep

ASJC Scopus subject areas

  • Nephrology


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