Effects of the L- and N-type calcium channel blocker cilnidipine on growth of vascular smooth muscle cells from spontaneously hypertensive rats

被引:7
作者
Hu, WY [1 ]
Fukuda, N [1 ]
Su, JZ [1 ]
Kanmatsuse, K [1 ]
机构
[1] Nihon Univ, Dept Internal Med 2, Sch Med, Dept Internal Med 2, Tokyo 1738610, Japan
关键词
spontaneously hypertensive rats; vascular smooth muscle; calcium antagonists; cilnidipine; growth factors;
D O I
10.1097/00005344-200109000-00013
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) show exaggerated growth compared with cells from Wistar-Kyoto (WKY) rats. Calcium antagonists have recently been reported to have an in vivo antiproliferative effect on hypertensive cardiovascular organs. We investigated the effects of the calcium antagonist cilnidipine that blocks both L- and N-type calcium channels on the growth of VSMC from SHR. Cilnidipine (1 and 10 muM significantly inhibited basal DNA synthesis in VSMC from both rat strains. the inhibition was significantly larger in VSMC from SHR than in cells from WKY rats, and was significantly greater than effects of nifedipine. Cilnidipine (1 muM) significantly inhibited serum-stimulated DNA synthesis in VSMC from both rat strains. The inhibition was more marked in VSMC from SHR than in cells from WKY rats. Angiotensin II, platelet-derived growth factor (PDGF)-AA. and phorbol-12-myristate-13-acetate dose-dependently increased DNA synthesis in VSMC from SHR but not in cells from WKY rats. Cilnidipine (1 muM) significantly suppressed this increase in DNA synthesis in VSMC from SHR. Expression of basic fibroblast growth factor (bFGF), transforming growth factor-beta1, and PDGF A-chain mRNAs was markedly greater in VSMC from SHR than in cells from WKY rats, Cilnidipine (I LM) significantly inhibited the expression of TGF-beta1 mRNA in VSMC from SHR but not in cells from WKY rats. These findings suggest that cilnidipine exerts its antiproliferative effects through the inhibition of DNA synthesis induced by growth-promoting factors and by inhibiting the expression of TGF-P I mRNA in VSMC from SHR.
引用
收藏
页码:450 / 459
页数:10
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