TY - JOUR
T1 - Involvement of Rho-kinase in vascular remodeling caused by long-term inhibition of nitric oxide synthesis in rats
AU - Ikegaki, Ichiro
AU - Hattori, Tsuyoshi
AU - Yamaguchi, Tamami
AU - Sasaki, Yasuo
AU - Satoh, Shin ichi
AU - Asano, Toshio
AU - Shimokawa, Hiroaki
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001/9/7
Y1 - 2001/9/7
N2 - Long-term inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular remodeling in rats. To determine the pathogenic mechanism involved in vascular remodeling, we examined the effects of fasudil, a Rho-kinase inhibitor, on vascular lesion formation. In rats treated with L-NAME at 10 mg/kg/day, vascular remodeling was evident in both large and small coronary arteries at the fourth week. Fasudil (3 mg/kg, p.o., twice daily) markedly prevented the development of vascular remodeling in small coronary arteries. Coronary flow was measured in Langendorff perfused isolated heart preparations. Long-term treatment with L-NAME caused a significant decrease in coronary flow, which was significantly inhibited by fasudil. Fasudil suppressed the structural and functional changes in coronary arteries by chronic blockade of NO synthesis. Thus, the Rho-kinase pathway may be substantially involved in the pathogenesis of vascular remodeling in this rat model.
AB - Long-term inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular remodeling in rats. To determine the pathogenic mechanism involved in vascular remodeling, we examined the effects of fasudil, a Rho-kinase inhibitor, on vascular lesion formation. In rats treated with L-NAME at 10 mg/kg/day, vascular remodeling was evident in both large and small coronary arteries at the fourth week. Fasudil (3 mg/kg, p.o., twice daily) markedly prevented the development of vascular remodeling in small coronary arteries. Coronary flow was measured in Langendorff perfused isolated heart preparations. Long-term treatment with L-NAME caused a significant decrease in coronary flow, which was significantly inhibited by fasudil. Fasudil suppressed the structural and functional changes in coronary arteries by chronic blockade of NO synthesis. Thus, the Rho-kinase pathway may be substantially involved in the pathogenesis of vascular remodeling in this rat model.
KW - Fasudil
KW - Hydroxyfasudil
KW - Nitric oxide (NO)
KW - Remodeling
KW - Rho-kinase
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U2 - 10.1016/S0014-2999(01)01181-5
DO - 10.1016/S0014-2999(01)01181-5
M3 - Article
C2 - 11553365
AN - SCOPUS:0035823041
VL - 427
SP - 69
EP - 75
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -