Evidence that angiotensin II, endothelins and nitric oxide regulate mitogen-activated protein kinase activity in rat aorta

被引:22
作者
Kubo, T [1 ]
Saito, E [1 ]
Hanada, M [1 ]
Kambe, T [1 ]
Hagiwara, Y [1 ]
机构
[1] Showa Coll Pharmaceut Sci, Dept Pharmacol, Machida, Tokyo 194, Japan
关键词
angiotensin; endothelin; nitric oxide (NO); aorta; rat; MAP (mitogen-activated protein) kinase;
D O I
10.1016/S0014-2999(98)00111-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We measured the activity of mitogen-activated protein (MAP) kinases, enzymes believed to be involved in the pathway for cell proliferation, in rat aortic strips with or without endothelium, and examined effects of angiotensin receptor antagonists, endothelin receptor antagonists and nitric oxide (NO)-related agents. Endothelium removal produced an activation of MAP kinase activity in the strips, whereas the enzyme activity was not affected in the adventitia. The MAP kinase activation was inhibited by either the angiotensin AT(1) receptor antagonist losartan or the endothelin ETA receptor antagonist BQ 123. The combination of both antagonists caused an additive inhibition. The angiotensin AT(2) receptor antagonist PD 123,319 and the endothelin ETB receptor antagonist BQ 788 did not affect the MAP kinase activation. The NO synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) caused an activation of MAP kinase in the endothelium-intact aorta and the MAP kinase activation was inhibited by losartan or BQ123. The NO releaser nitroprusside inhibited the MAP kinase activation induced by endothelium removal or angiotensin II. These results suggest that even in isolated arteries, NO of endothelial origin tonically exert MAP kinase-inhibiting effects and endogenous angiotensin II and endothelins in the media are tonically released to cause MAP kinase-stimulating effects in medial smooth muscle. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:337 / 346
页数:10
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