Remiszewski Patryk, Malinowska Barbara
Department of Experimental Physiology and Pathophysiology, Medical University of Bialystok, Mickiewicza Str. 2A, 15-222 Białystok, Poland.
Pharmaceuticals (Basel). 2022 Sep 7;15(9):1119. doi: 10.3390/ph15091119.
Systemic and pulmonary hypertension are multifactorial, high-pressure diseases. The first one is a civilizational condition, and the second one is characterized by a very high mortality rate. Searching for new therapeutic strategies is still an important task. (Endo)cannabinoids, known for their strong vasodilatory properties, have been proposed as possible drugs for different types of hypertension. Unfortunately, our review, in which we summarized all publications found in the PubMed database regarding chronic administration of (endo)cannabinoids in experimental models of systemic and pulmonary hypertension, does not confirm any encouraging suggestions, being based mainly on in vitro and acute in vivo experiments. We considered vasodilator or blood pressure (BP) responses and cardioprotective, anti-oxidative, and the anti-inflammatory effects of particular compounds and their influence on the endocannabinoid system. We found that multitarget (endo)cannabinoids failed to modify higher BP in systemic hypertension since they induced responses leading to decreased and increased BP. In contrast, multitarget cannabidiol and monotarget ligands effectively treated pulmonary and systemic hypertension, respectively. To summarize, based on the available literature, only (endo)cannabinoids with a defined site of action are recommended as potential antihypertensive compounds in systemic hypertension, whereas both mono- and multitarget compounds may be effective in pulmonary hypertension.
系统性高血压和肺动脉高压是多因素导致的高压疾病。前者是一种文明病，后者的特点是死亡率极高。寻找新的治疗策略仍然是一项重要任务。（内源性）大麻素以其强大的血管舒张特性而闻名，已被提议作为治疗不同类型高血压的可能药物。不幸的是，我们的综述总结了在PubMed数据库中找到的所有关于在系统性和肺动脉高压实验模型中长期给予（内源性）大麻素的出版物，并未证实任何令人鼓舞的建议，这些建议主要基于体外和急性体内实验。我们考虑了特定化合物的血管舒张或血压（BP）反应以及心脏保护、抗氧化和抗炎作用及其对内源性大麻素系统的影响。我们发现多靶点（内源性）大麻素未能改变系统性高血压中的较高血压，因为它们诱导的反应导致血压降低和升高。相比之下，多靶点大麻二酚和单靶点配体分别有效治疗了肺动脉高压和系统性高血压。总之，根据现有文献，在系统性高血压中，只有具有明确作用位点的（内源性）大麻素被推荐作为潜在的抗高血压化合物，而单靶点和多靶点化合物在肺动脉高压中可能都有效。
