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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. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate how endocannabinoids interact with excitotoxic processes both in vitro, using primary neural cell cultures, and in vivo, in the TMEV-IDD model of multiple sclerosis. First, we observed that neuronal cells respond to excitotoxic challenges by the production of endocannabinoid molecules which in turn exerted neuroprotective effects against excitotoxicity. The inhibitor of endocannabinoid uptake, UCM707, protected specifically against AMPA-induced excitotoxicity, by activating CB1 and CB2 cannabinoid receptors, as well as the nuclear factor, PPARγ. This neuroprotective effect was reverted by blocking the glial glutamate transporter, GLT-1. Mice subjected to the model of multiple sclerosis showed a decrease in the expression of GLT-1. UCM707 reversed this loss of GLT-1 and induced a therapeutic effect. Our data indicate that the enhancement of the endocannabinoid tone leads to neuroprotection against AMPA-induced excitotoxicity and provides therapeutic effects in this model of multiple sclerosis.