Inhibitory effect of a novel angiotensin II type 1 receptor antagonist RNH-6270 on growth of vascular smooth muscle cells from spontaneously hypertensive rats: Different anti-proliferative effect to angiotensin-converting enzyme inhibitor

被引：11
作者：
Teng, J [1 ]
Fukuda, N [1 ]
Suzuki, R [1 ]
Takagi, H [1 ]
Ikeda, Y [1 ]
Tahira, Y [1 ]
Kanmatsuse, K [1 ]
机构：
[1] Nihon Univ, Sch Med, Dept Internal Med 2, Itabashi Ku, Tokyo 1738610, Japan
来源：
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY | 2002年 / 39卷 / 02期
关键词：
angiotensin II; angiotensin II type 1 receptor antagonist; angiotensin-converting enzyme inhibitor; cell proliferation; growth factor; spontaneously hypertensive rat; vascular smooth muscle cell;
D O I：
10.1097/00005344-200202000-00002
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
The current study was undertaken to evaluate the anti-proliferative effect of a novel angiotensin II type 1 (AT1) receptor antagonist, RNH-6270, on exaggerated growth of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR), in comparison with the effects of an angiotensin-converting enzyme (ACE) inhibitor. RNH-6270 and temocapril significantly inhibited basal DNA synthesis in VSMCs from SHRs in a dose-dependent manner, but not in cells from Wistar-Kyoto (WKY) rats. SHR-derived VSMC showed a hyperresponse of DNA synthesis to serum and angiotensin II compared with that of WKY rats-derived VSMC. RNH-6270 did not affect serum-stimulated DNA synthesis in VSMCs from both rat strains. RNH-6270 abolished angiotensin II-stimulated DNA synthesis in VSMC from both rat strains. RNH-6270 significantly inhibited proliferation of VSMC from both rat strains, but the ACE inhibitor temocapril did not exert such an effect. RNH-6270 decreased the specific binding of angiotensin II to VSMC in a competitive manner for angiotensin II receptors in both rat strains. RNH-6270 and temocapril significantly decreased the expression of growth factor mRNAs and proteins in VSMC from SHR, but not in cells from WKY rats. These results suggest that RNH-6270 is a potent AT1 receptor antagonist and has anti-proliferative effects on VSMCs from SHR, which was not seen with an ACE inhibitor. The growth inhibitory effect of RNH-6270 may be associated with the inhibition of growth factors via antagonism to AT1 receptors.
引用
收藏
页码：161 / 171
页数：11
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