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钾通道开放药物克罗卡林可使健康志愿者上肢产生动脉选择性血管舒张。

The potassium channel opening drug cromakalim produces arterioselective vasodilation in the upper limbs of healthy volunteers.

作者信息

Webb D J, Benjamin N, Vallance P

机构信息

Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London.

出版信息

Br J Clin Pharmacol. 1989 Jun;27(6):757-61. doi: 10.1111/j.1365-2125.1989.tb03437.x.

DOI:10.1111/j.1365-2125.1989.tb03437.x
PMID:2757892
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1379802/
Abstract
  1. The effect of the K+ channel opening drug cromakalim on forearm blood flow during direct infusion into the brachial artery, and on the size of noradrenaline preconstricted hand veins during infusion directly into the vein, was studied in eight healthy volunteers. 2. Cromakalim (0.01-10.0 micrograms min-1) produced a dose-dependent increase in blood flow in the infused forearm, from 5.4 +/- 2.5 to 15.1 +/- 7.3 ml 100 ml-1 forearm min-1 at 10 micrograms min-1 (P less than 0.001). The half-time of offset of its action was 30 min. There was no change in blood flow in the non-infused forearm. 3. There was no increase in the size of noradrenaline pre-constricted dorsal veins during local infusion of cromakalim (0.001-1.0 microgram min-1). Glyceryl trinitrate (0.4 microgram min-1) however, completely reversed the constriction to noradrenaline (P less than 0.001). 4. The clear arterioselectivity of cromakalim, as with other members of this new class of drug, accords with the dependency of venoconstriction on receptor-operated, rather than potential-operated mechanisms which are of importance in resistance vessels. With this haemodynamic profile cromakalim may prove of value in the treatment of arterial hypertension.
摘要
  1. 在8名健康志愿者中,研究了钾通道开放药物克罗卡林在直接注入肱动脉时对前臂血流的影响,以及在直接注入静脉时对去甲肾上腺素预收缩手部静脉大小的影响。2. 克罗卡林(0.01 - 10.0微克/分钟)使注入的前臂血流呈剂量依赖性增加,在10微克/分钟时,从5.4±2.5增加到15.1±7.3毫升/100毫升前臂/分钟(P<0.001)。其作用消退的半衰期为30分钟。未注入药物的前臂血流无变化。3. 局部注入克罗卡林(0.001 - 1.0微克/分钟)期间,去甲肾上腺素预收缩的手背静脉大小没有增加。然而,硝酸甘油(0.4微克/分钟)可完全逆转去甲肾上腺素引起的收缩(P<0.001)。4. 与这类新药的其他成员一样,克罗卡林具有明显的动脉选择性,这与静脉收缩依赖于受体介导机制而非对阻力血管起重要作用的电位介导机制相一致。基于这种血流动力学特征,克罗卡林可能在动脉高血压治疗中具有价值。

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