Antiplatelet effect of amlodipine - A possible mechanism through a nitric oxide,mediated process

被引:22
作者
Chou, TC
Li, CY
Yen, MH
Ding, YA
机构
[1] Tri Serv Gen Hosp, Grad Inst Med Sci, Natl Def Med Ctr, Taipei, Taiwan
[2] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Anesthesiol, Taipei, Taiwan
[3] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Pharmacol, Taipei, Taiwan
[4] Vet Gen Hosp Taipei, Dept Cardiol, Taipei, Taiwan
关键词
amlodipine; nitric oxide; guanosine; 3; 5 '-cyclic monophosphate; thromboxane B-2; platelet aggregation;
D O I
10.1016/S0006-2952(99)00235-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effect of amlodipine, a novel calcium channel blocker of the dihydropyridine type, on rabbit platelet aggregation, and the possible antiaggregatory mechanisms of amlodipine, especially on the nitric oxide (NO) guanosine 3',5'-cyclic monophosphate (cyclic GMP)-mediated pathway, were investigated. Other effects of amlodipine on thromboxane B-2 (TXB2) formation in platelets also were examined. Amlodipine concentration-dependently inhibited rabbit platelet aggregation induced by collagen (10 mu g/mL) or thrombin (0.1 U/mL) with an IC50 range of 32-69 mu M. Along with this inhibition, our results also demonstrated that in the presence of L-arginine (100 mu M), amlodipine (50 mu M) increased nitric oxide synthetase (NOS) activity (from the resting activity of 2.05 +/- 0.36 to 7.11 +/- 0.95 pmol/mg protein/min) and NO release (by 80%), accompanied by an elevation of the cyclic GMP level (from the resting platelet level of 1.27 +/- 0.12 to 6.21 +/- 0.55 pmol/10(9) platelets) induced by collagen (10 mu g/mL). However, the antiaggregatory effect of amlodipine (50 mu M) could be attenuated significantly by oxyhemoglobin (5 mu M), a NO scavenger, or NG-nitro-L-arginine methyl ester (100 mu M), a specific NOS inhibitor. In addition, the TXB2 production in platelets induced by collagen or thrombin was concentration-dependently inhibited by amlodipine. Therefore, we propose that: the antiaggregatory mechanisms of amlodipine might be mediated, in part, by a NO-cyclic GMP process accompanied by the inhibition of TXB2 formation in platelets. (C) 1999 Elsevier Science Inc.
引用
收藏
页码:1657 / 1663
页数:7
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