Why Multitarget Vasodilatory (Endo)cannabinoids Are Not Effective as Antihypertensive Compounds after Chronic Administration: Comparison of Their Effects on Systemic and Pulmonary Hypertension

Abstract

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.

Endocannabinoid system: An untold story in hypertensive nephropathy

“…Massive amount of data is witness for therapeutic role of ECS in hypertension [33][34][35][36][37]. Main reasons that support substantial role of ECS in hypertension is based upon three aspects:…”

LC-MS Fingerprinting Development for Standardized Precipitate from Agastache mexicana, Which Induces Antihypertensive Effect through NO Production and Calcium Channel Blockade

“…The hypertension is a risk factor for developing renal dysfunction, cerebrovascular disease, heart failure, and stroke. This has a global epidemiological and economic impact [ 2 , 3 , 4 ]. Even though there are many antihypertensive drugs such as diuretics, vasodilators, sympatholytic, calcium-channel blockers, and drugs that inhibit the renin-angiotensin system, these are often not devoid of side effects and non-adherence to therapy is a common issue among patients [ 3 , 4 , 5 ].…”

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