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维拉帕米对兔套环颈动脉内膜增厚及血管反应性的影响。

Effect of verapamil on intimal thickening and vascular reactivity in the collared carotid artery of the rabbit.

作者信息

Ustünes L, Yasa M, Kerry Z, Ozdemir N, Berkan T, Erhan Y, Ozer A

机构信息

Department of Parmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey.

出版信息

Br J Pharmacol. 1996 Aug;118(7):1681-8. doi: 10.1111/j.1476-5381.1996.tb15592.x.

Abstract
  1. Intimal thickening is a common site for atherosclerosis. Therefore, we investigated whether the calcium entry blocker verapamil (10 mg kg-1 body weight day-1, s.c.) can retard intimal thickening and changes in vascular reactivity induced by a non-occlusive, silicone collar positioned around the left carotid artery of rabbits. The contralateral carotid artery was sham-operated and served as a control. 2. Verapamil and placebo (saline 0.1 ml kg-1, day-1, s.c.) treatments were initiated 7 days before placing the collar and lasted 3 weeks. Thereafter, segments were cut from collared and sham-treated arteries for histology and isometric tension recording. 3. The intima/media (I/M ratio increased after 14 days of collar treatment, but intimal thickening was not inhibited by verapamil (I/M ratio placebo 0.31 +/- 0.07, verapamil 0.32 +/- 0.09). 4. The collar decreased the capacity to develop force, as indicated by the response to a supramaximal concentration of KCl, decreased the sensitivity (pD2) to acetylcholine (ACh) and phenylephrine (Phe), but increased the sensitivity to 5-hydroxytryamine (5-HT). 5. Although verapamil did not affect intimal thickening, it normalized the hypersensitivity to 5-HT in collared arteries. 6. The contraction to the supramaximal concentration of KCl was not affected by verapamil. Verapamil decreased the Emax of ACh, but this was only seen in collar-treated arteries. Verapamil also decreased the sensitivity to ACh and Phe, in both sham- and collar-treated arteries. 7. We conclude that verapamil, without preventing thickening of the intima, can modify collar-induced changes in vascular reactivity.
摘要
  1. 内膜增厚是动脉粥样硬化的常见部位。因此,我们研究了钙通道阻滞剂维拉帕米(10毫克/千克体重/天,皮下注射)是否能延缓内膜增厚以及由置于兔左颈动脉周围的非阻塞性硅胶环引起的血管反应性变化。对侧颈动脉进行假手术作为对照。2. 在放置硅胶环前7天开始维拉帕米和安慰剂(0.1毫升/千克体重/天,皮下注射)治疗,持续3周。此后,从放置硅胶环和假手术处理的动脉中切取节段进行组织学检查和等长张力记录。3. 放置硅胶环14天后内膜/中膜(I/M)比值增加,但维拉帕米并未抑制内膜增厚(安慰剂组I/M比值为0.31±0.07,维拉帕米组为0.32±0.09)。4. 硅胶环降低了对最大浓度氯化钾的反应所显示的产生力量的能力,降低了对乙酰胆碱(ACh)和去氧肾上腺素(Phe)的敏感性(pD₂),但增加了对5-羟色胺(5-HT)的敏感性。5. 虽然维拉帕米不影响内膜增厚,但它使放置硅胶环动脉对5-HT的高敏反应恢复正常。6. 对最大浓度氯化钾的收缩反应不受维拉帕米影响。维拉帕米降低了ACh的最大效应(Emax),但仅在放置硅胶环处理的动脉中可见。维拉帕米还降低了假手术和放置硅胶环处理的动脉对ACh和Phe的敏感性。7. 我们得出结论,维拉帕米在不阻止内膜增厚的情况下,可以改变硅胶环引起的血管反应性变化。

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