Atherosclerosis is the leading cause of vascular disease worldwide and contributes significantly to deaths from cardiovascular complications. There is a remarkably close relationship between atherosclerotic plaque formation and the activation of renin-angiotensin system (RAS). However, depending on which RAS pathway is activated, pro-or anti-atherogenic outcomes may be observed. This brief review focuses on the role of three of the most important pieces of RAS axis, angiotensin II (Ang-II), angiotensin converting enzyme type 2 (ACE2), and angiotensin 1-7 (Ang-1-7) and their involvement in atherosclerosis. We focused on the effects of these molecules on vascular function and inflammation, which are important determinants of atherogenesis. Furthermore, we highlighted potential pharmacological approaches to treat this disorder.

A prática da atenção farmacêutica no acompanhamento farmacoterapêutico de idosos diabéticos e hipertensos: relato de caso The practice of pharmaceutical attention in pharmacotherapeutic monitoring of diabetic and hypertensive elderly: case report

This work aimed to explore the cardiovascular effects induced by freeze-dried juice from Syzygium jambolanum (Lam.) DC fruits (JSJ). JSJ presented high polyphenol content and steroids. HPLC analysis revealed that 2,5-dihydroxybenzoic and caffeic acid were present in higher amounts in the JSJ extract. In rat, JSJ induces hypotension and vasodilatation in mesenteric arteries, with or without vascular endothelium. JSJ-mediated vasodilation response against contractions induced with KCl (60 mM) depolarizing solution was significantly lower than the responses induced by JSJ when evaluated against phenylephrine-induced contractions. To investigate the involvement of potassium channels we used Tyrode's solution with KCl (20 mM) or tetraethylammonium (1.0, 3.0, or 5.0 mM). In these conditions JSJ-induced effects were significantly attenuated. To investigate the potassium channel subtypes involved in the response, we used 4-aminopyridine, glibenclamide, BaCl2, and iberiotoxin. In the presence (simultaneous) of different potassium channel blockers we observed a significant attenuation of JSJ-induced effect. Inhibition was also observed when using BaCl2, glibenclamide, or 4-aminopyridine, separately. However, incubation with iberiotoxin did not promote changes in either maximum effect, or potency. We also evidenced a discrete participation of CaV channels in the JSJ-induced vasorelaxant effect. In addition, patch-clamp studies demonstrated that JSJ could activate potassium channels. In conclusion, JSJ promotes hypotension and vasorelaxation in rats, involving, at least, the activation of potassium channels.

ResumoA hipertensão arterial é uma das principais causas de morte em países desenvolvidos e em desenvolvimento, causando um grande impacto na saúde humana. O estresse oxidativo tem sido apontado como um mecanismo fundamental na hipertensão arterial dependente de angiotensina II, uma vez que modula a função barorreflexa em vários processos de fisiopatológicos. O presente trabalho teve como objetivo a realização de uma revisão de literatura abordando os recentes mecanismos que promovem alterações da hipertensão arterial dependente de angiotensina II. Foram enfatizados dois modelos dependentes de angiotensina II: dois-rins-um-clipe (2R1C) e desoxicorticosterona (DOCA-sal). A pesquisa corresponde a uma revisão bibliográfica de caráter descritivo, baseada na literatura científica atual, pesquisada em várias bases de dados. Estudos corroboram a hipótese que a angiotensina II é um dos principais agentes envolvidos no desenvolvimento da hipertensão arterial e que o aumento desse peptídeo é multifatorial, podendo induzir, em especial, o aumento do estresse oxidativo que, por sua vez, promove alterações em uma metaloprotease 17 (ADAM17) e disfunções na enzima conversora da angiotensina 2 (ECA2). Assim, novas ferramentas que induzam a diminuição do estresse oxidativo promovem efeitos benéficos, constituindo novos alvos terapêuticos na prevenção e tratamento de hipertensão arterial. Palavras-chave:Hipertensão, Angiotensina II, ECA 2, estresse oxidativo. Physiological aspects of angiotensin II-dependent hypertension: an overviewAbstract Hypertension is one of the main causes of death in developed and developing countries, inducing great impact in human health. Oxidative stress has been implicated as a key mechanism in Angiotensin II-dependent hypertension, since it modulates the baroreflex function in many pathophysiological processes. This study aimed to conduct a literature review addressing the recent mechanisms that promote changes in Angiotensin II-dependent hypertension. Here we highlighted two Angiotensin IIdependent hypertension models: two kidney-one-clip (2K1C) and deoxycorticosterone (DOCA-salt) hypertension. Bases on latest studies presented in important data base, it is possible to suggest that Angiotensin II is one of the main agents in hypertension development and the increase of this peptide is derived by multiple causes, which, in particular, acts as an inductor in oxidative stress production, in turn, it induces changes in a metalloprotease 17 (ADAM-17) and disruption of ACE2 compensatory activity. Thus, new tools that induce a reduction of oxidative stress promote beneficial effects, providing novel therapeutic targets to prevent and treat the Angiotensin II-dependent hypertension.

A Disintegrin and Metalloprotease 17 (ADAM17), also called tumor necrosis factor-ɑ (TNF-ɑ) convertase (TACE), is a well-known protease involved in the sheddase of growth factors, chemokines and cytokines. ADAM17 is also enrolled in hypertension, especially by shedding of angiotensin converting enzyme type 2 (ACE2) leading to impairment of angiotensin 1–7 [Ang-(1–7)] production and injury in vasodilation, induction of renal damage and cardiac hypertrophy. Activation of Mas receptor (MasR) by binding of Ang-(1–7) induces an increase in the nitric oxide (NO) gaseous molecule, which is an essential factor of vascular homeostasis and blood pressure control. On the other hand, TNF-ɑ has demonstrated to stimulate a decrease in nitric oxide bioavailability, triggering a disrupt in endothelium-dependent vasorelaxation. In spite of the previous studies, little knowledge is available about the involvement of the metalloprotease 17 and the NO pathways. Here we will provide an overview of the role of ADAM17 and Its mechanisms implicated with the NO formation.