Rapoport R M, Bevan J A
Blood Vessels. 1983;20(1):44-55. doi: 10.1159/000158458.
The purpose of this study was to investigate the effect of prior agonist-induced contraction of vascular smooth muscle on its subsequent responsiveness and maximum contractility. Repeated exposure of the rabbit ear artery to equieffective histamine (Hist) or KCl concentrations increased subsequent norepinephrine (NE) responsiveness and maximum contractility in comparison to rested controls. Tissues exposed in a similar manner to an equieffective serotonin concentration responded to NE more than did controls, but less than Hist- and KCl-pretreated tissues. Prior exposure to NE or KCl increased Hist responsiveness and maximum contractility. However, NE pretreatment did not increase serotonin or KCl responsiveness. The increased responsiveness and maximum contractility lasted for at least 90 and 390 min., respectively. When ear arteries were exposed to agonists in the presence of NaNO2 or papaverine the increase in responsiveness was either reduced or absent. Everted arteries repeatedly exposed to Hist demonstrated an increased tonic phase contraction to NE; there was no change in the initial transient phase of contraction. Exposure of the saphenous vein to Hist oe KCl had no effect on subsequent NE responsiveness; however, maximum contractility was increased. The present results suggest that (1) contraction brought about by agonist drugs can result in two separate phenomena -- increased responsiveness and increased maximum contractility; (2) the increased responsiveness may mask underlying alpha-adrenoceptor desensitization which may be agonist specific; (3) an event following agonist-receptor binding is responsible for increased responsiveness and increased maximum contractility; (4) the mechanism for increased responsiveness may be due to an increased coupling between receptor activation and membrane permeability to calcium; (5) agonist contraction in the saphenous vein and ear artery may be regulated by different mechanisms.
本研究的目的是探讨血管平滑肌预先由激动剂诱导的收缩对其随后反应性和最大收缩力的影响。与静息对照组相比，兔耳动脉反复暴露于等效组胺（Hist）或氯化钾浓度下，会增加随后去甲肾上腺素（NE）的反应性和最大收缩力。以类似方式暴露于等效血清素浓度的组织对NE的反应比对照组更大，但小于经Hist和氯化钾预处理的组织。预先暴露于NE或氯化钾会增加对Hist的反应性和最大收缩力。然而，NE预处理并未增加对血清素或氯化钾的反应性。反应性增加和最大收缩力增加分别持续至少90分钟和390分钟。当耳动脉在存在亚硝酸钠或罂粟碱的情况下暴露于激动剂时，反应性的增加会降低或消失。反复暴露于Hist的翻转动脉对NE的紧张相收缩增加；收缩的初始瞬态相没有变化。隐静脉暴露于Hist或氯化钾对随后NE的反应性没有影响；然而，最大收缩力增加。目前的结果表明：（1）激动剂药物引起的收缩可导致两种不同的现象——反应性增加和最大收缩力增加；（2）反应性增加可能掩盖了潜在的α-肾上腺素能受体脱敏，而这种脱敏可能具有激动剂特异性；（3）激动剂与受体结合后的一个事件是反应性增加和最大收缩力增加的原因；（4）反应性增加的机制可能是由于受体激活与膜对钙的通透性之间的偶联增加；（5）隐静脉和耳动脉中的激动剂收缩可能受不同机制调节。
