Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden Gelugor 11800, Penang, Malaysia.
Int J Mol Sci. 2018 Jan 2;19(1):120. doi: 10.3390/ijms19010120.
Hypertension is asymptomatic and a well-known "silent killer", which can cause various concomitant diseases in human population after years of adherence. Although there are varieties of synthetic antihypertensive drugs available in current market, their relatively low efficacies and major application in only single drug therapy, as well as the undesired chronic adverse effects associated, has drawn the attention of worldwide scientists. According to the trend of antihypertensive drug evolution, the antihypertensive drugs used as primary treatment often change from time-to-time with the purpose of achieving the targeted blood pressure range. One of the major concerns that need to be accounted for here is that the signaling mechanism pathways involved in the vasculature during the vascular tone regulation should be clearly understood during the pharmacological research of antihypertensive drugs, either in vitro or in vivo. There are plenty of articles that discussed the signaling mechanism pathways mediated in vascular tone in isolated fragments instead of a whole comprehensive image. Therefore, the present review aims to summarize previous published vasculature-related studies and provide an overall depiction of each pathway including endothelium-derived relaxing factors, G-protein-coupled, enzyme-linked, and channel-linked receptors that occurred in the microenvironment of vasculature with a full schematic diagram on the ways their signals interact. Furthermore, the crucial vasodilative receptors that should be included in the mechanisms of actions study on vasodilatory effects of test compounds were suggested in the present review as well.
高血压是无症状的，是一种众所周知的“沉默杀手”，它可以在人类多年的坚持后引起各种伴发性疾病。尽管目前市场上有各种合成降压药物，但它们的疗效相对较低，主要应用于单一药物治疗，以及相关的慢性不良作用，引起了全球科学家的关注。根据降压药物的进化趋势，作为主要治疗手段的降压药物经常随着时间的推移而变化，目的是达到目标血压范围。这里需要考虑的一个主要问题是，在降压药物的药理学研究中，无论是在体外还是在体内，都应该清楚地了解血管张力调节中涉及的信号机制途径。有大量的文章讨论了在分离片段中介导血管张力的信号机制途径，而不是一个全面的综合图像。因此，本综述旨在总结以前发表的与血管有关的研究，并提供每个途径的全面描述，包括内皮衍生的松弛因子、G 蛋白偶联、酶联和通道偶联受体，这些途径发生在血管的微环境中，并附有信号相互作用的全示意图。此外，本综述还建议在测试化合物的血管舒张作用的作用机制研究中纳入关键的血管舒张受体。
