HIGH GLUCOSE AUGMENTS ANGIOTENSIN-II ACTION BY INHIBITING NO SYNTHESIS IN IN-VITRO MICROPERFUSED RABBIT AFFERENT ARTERIOLES

被引:31
作者
ARIMA, S [1 ]
ITO, S [1 ]
OMATA, K [1 ]
TAKEUCHI, K [1 ]
ABE, K [1 ]
机构
[1] TOHOKU UNIV, SCH MED, DEPT INTERNAL MED 2, SENDAI, MIYAGI 98077, JAPAN
关键词
D O I
10.1038/ki.1995.338
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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; HG(30)-Af-Arts) of glucose, and then vascular reactivity was examined. Sensitivity to angiotensin II (Ang II) was significantly higher in HG(30)-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(-11) M in HG(30)-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 HG(30)-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 HG(30)-Af-Arts, suggesting impaired NO synthesis in HG(30)-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 HG(30)-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.
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页码:683 / 689
页数:7
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