School of Graduate Entry Medicine and Health, University of Nottingham, Royal Derby Hospital, Derby, UK.
Br J Pharmacol. 2014 Mar;171(6):1361-78. doi: 10.1111/bph.12560.
Application of cannabinoids and endocannabinoids to perfused vascular beds or individual isolated arteries results in changes in vascular resistance. In most cases, the result is vasorelaxation, although vasoconstrictor responses are also observed. Cannabinoids also modulate the actions of vasoactive compounds including acetylcholine, methoxamine, angiotensin II and U46619 (thromboxane mimetic). Numerous mechanisms of action have been proposed including receptor activation, potassium channel activation, calcium channel inhibition and the production of vasoactive mediators such as calcitonin gene-related peptide, prostanoids, NO, endothelial-derived hyperpolarizing factor and hydrogen peroxide. The purpose of this review is to examine the evidence for the range of receptors now known to be activated by cannabinoids. Direct activation by cannabinoids of CB1 , CBe , TRPV1 (and potentially other TRP channels) and PPARs in the vasculature has been observed. A potential role for CB2, GPR55 and 5-HT1 A has also been identified in some studies. Indirectly, activation of prostanoid receptors (TP, IP, EP1 and EP4 ) and the CGRP receptor is involved in the vascular responses to cannabinoids. The majority of this evidence has been obtained through animal research, but recent work has confirmed some of these targets in human arteries. Vascular responses to cannabinoids are enhanced in hypertension and cirrhosis, but are reduced in obesity and diabetes, both due to changes in the target sites of action. Much further work is required to establish the extent of vascular actions of cannabinoids and the application of this research in physiological and pathophysiological situations.
This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6.
将大麻素和内源性大麻素应用于灌流血管床或单个分离的动脉会导致血管阻力发生变化。在大多数情况下，结果是血管舒张，尽管也观察到血管收缩反应。大麻素还调节包括乙酰胆碱、甲氧胺、血管紧张素 II 和 U46619（血栓素模拟物）在内的血管活性化合物的作用。已经提出了许多作用机制，包括受体激活、钾通道激活、钙通道抑制以及产生血管活性介质，如降钙素基因相关肽、前列腺素、NO、内皮衍生超极化因子和过氧化氢。本综述的目的是检查目前已知被大麻素激活的受体范围的证据。已经观察到大麻素直接激活 CB1、CBe、TRPV1（和潜在的其他 TRP 通道）和血管中的 PPAR。在一些研究中，还确定了 CB2、GPR55 和 5-HT1A 的潜在作用。间接地，前列腺素受体（TP、IP、EP1 和 EP4）和 CGRP 受体的激活参与了大麻素对血管的反应。这些证据中的大部分是通过动物研究获得的，但最近的工作已经在人类动脉中证实了其中的一些靶点。大麻素对血管的反应在高血压和肝硬化中增强，但在肥胖和糖尿病中降低，这两者都是由于作用靶点的变化所致。需要进一步开展工作以确定大麻素对血管的作用程度以及将这项研究应用于生理和病理生理情况。
本文是关于大麻素 2013 年主题部分的一部分。要查看本节中的其他文章，请访问 http://dx.doi.org/10.1111/bph.2014.171.issue-6。
