TY - JOUR
T1 - High glucose augments angiotensin II action by inhibiting NO synthesis in in vitro microperfused rabbit afferent arterioles
AU - Arima, Shuji
AU - Ito, Sadayoshi
AU - Omata, Ken
AU - Takeuchi, Kazuhisa
AU - Abe, Keishi
N1 - Funding Information:
Sessions (1994, Chicago). This work was supported in part by grants from the Ministry of Science, Education and Culture, Japan (No. 05454338 and No. 06671124), and a grant for Renal Diseases (Kurokawa-han) from the Ministry of Health and Welfare, Japan. The authors thank Miss Hiromi Takahashi and Miss Sachiko Matsumoto for their secretarial and experi- mental assistance.
PY - 1995/9
Y1 - 1995/9
N2 - 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.
AB - 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.
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U2 - 10.1038/ki.1995.338
DO - 10.1038/ki.1995.338
M3 - Article
C2 - 7474652
AN - SCOPUS:0029126282
VL - 48
SP - 683
EP - 689
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 3
ER -