Comparative effects of azelnidipine and other Ca2+-channel blockers on the induction of inducible nitric oxide synthase in vascular smooth muscle cells

被引：24

作者：

Ma, X ^{[1
]}

Kishida, S ^{[1
]}

Wang, GQ ^{[1
]}

Meguro, K ^{[1
]}

Imuta, H ^{[1
]}

Oonuma, H ^{[1
]}

Iida, H ^{[1
]}

Jo, T ^{[1
]}

Takano, H ^{[1
]}

Morita, T ^{[1
]}

Nagai, K ^{[1
]}

Nakajima, T ^{[1
]}

机构：

[1] Univ Tokyo, Dept Cardiovasc Med & Resp Med, Tokyo, Japan

来源：

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY | 2006年 / 47卷 / 02期

关键词：

azelnidipine; calcium-channel blocker; endothelial nitric oxide synthase; inducible nitric oxide synthase; nitric oxide;

D O I：

10.1097/01.fjc.0000205497.90765.b0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Overproduction of nitric oxide by inducible nitric oxide synthase contributes to the progression of cardiovascular disease. We investigated the effects of azelnidipine and other Ca2+-channel blockers oil nitric oxide production by cultured aortic smooth muscle cells isolated from Wistar rats and human umbilical vein endothelial cells (HUVECs), using the Griess reaction and oxyhemoglobin method. Release of lactic dehydrogenase (LDH) was measured to evaluate cell damage, and immunohistochemistry was performed to examine the expression of inducible nitric oxide synthase and nitrotyrosine protein. Azelnidipine and other Ca2+-channel blockers inhibited the release of nitric oxide induced by lipopolysaccharide plus interferon-gamma. Azelnidipine inhibited it most potently among the Ca2+-channel blockers tested (azelnidipine, amlodipine, nifedipine, diltiazem, verapamil, and micardipine) at a concentration of 10 mu M. Longer stimulation with these agents induced the expression of inducible nitric oxide synthase and nitrotyrosine, with all increase of lactic dehydrogenase release, whereas azelnidipine Suppressed these changes. In human umbilical vein endothelial cells, azelnidipine enhanced basal nitric oxide production by endothelial nitric oxide synthase. In conclusion, azelnidipine potently inhibited the induction of inducible nitric oxide synthase and then nitric oxide production ill vascular smooth muscle cells, while enhancing constitutive nitric oxide production by endothelial cells. Azelnidipine may inhibit nitrotyrosine expression and cell damage caused by overproduction of nitric oxide, suggesting a mechanism for its cardiovascular protective effect.

引用

页码：314 / 321

页数：8

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