Mendizábal V E, Adler-Graschinsky E
Instituto de Investigaciones Farmacológicas (CONICET), Buenos Aires, Argentina.
Br J Pharmacol. 2007 Jun;151(4):427-40. doi: 10.1038/sj.bjp.0707261. Epub 2007 Apr 23.
In addition to their classical known effects, such as analgesia, impairment of cognition and learning and appetite enhancement, cannabinoids have also been related to the regulation of cardiovascular responses and implicated in cardiovascular pathology. Elevated levels of endocannabinoids have been related to the extreme hypotension associated with various forms of shock as well as to the cardiovascular abnormalities that accompany cirrhosis. In contrast, cannabinoids have also been associated with beneficial effects on the cardiovascular system, such as a protective role in atherosclerosis progression and in cerebral and myocardial ischaemia. In addition, it has also been suggested that the pharmacological manipulation of the endocannabinoid system may offer a novel approach to antihypertensive therapy. During the last decades, the tremendous increase in the understanding of the molecular basis of cannabinoid activity has encouraged many pharmaceutical companies to develop more potent synthetic cannabinoid analogues and antagonists, leading to an explosion of basic research and clinical trials. Consequently. not only the synthetic THC dronabinol (Marinol) and the synthetic THC analogue nabilone (Cesamet) have been approved in the United States, but also the standardized cannabis extract (Sativex) in Canada. At least three strategies can be foreseen in the future clinical use of cannabinoid-based drugs: (a) the use of CB(1) receptor antagonists, such as the recently approved rimonabant (b) the use of CB(2)-selective agonists, and (c) the use of inhibitors of endocannabinoid degradation. In this context, the present review examines the effects of cannabinoids and of the pharmacological manipulation of the endocannabinoid system, in cardiovascular pathophysiology.
除了其已知的经典作用，如镇痛、损害认知和学习以及增强食欲外，大麻素还与心血管反应的调节有关，并涉及心血管病理学。内源性大麻素水平升高与各种形式休克相关的极端低血压以及肝硬化伴随的心血管异常有关。相反，大麻素也与对心血管系统的有益作用有关，如在动脉粥样硬化进展以及脑和心肌缺血中起保护作用。此外，也有人提出对内源性大麻素系统进行药理学调控可能为抗高血压治疗提供一种新方法。在过去几十年里，对大麻素活性分子基础的认识大幅增加，促使许多制药公司开发更有效的合成大麻素类似物和拮抗剂，引发了基础研究和临床试验的激增。因此，不仅合成四氢大麻酚屈大麻酚（ Marinol）和合成四氢大麻酚类似物纳布隆（ Cesamet）在美国已获批准，加拿大的标准化大麻提取物（ Sativex）也已获批。在未来基于大麻素的药物临床应用中至少可预见三种策略：（ a）使用 CB(1)受体拮抗剂，如最近获批的利莫那班；（ b）使用 CB(2)选择性激动剂；以及（ c）使用内源性大麻素降解抑制剂。在此背景下，本综述探讨了大麻素以及内源性大麻素系统的药理学调控在心血管病理生理学中的作用。
