RESUMO
The renin-angiotensin system (RAS) is a classical hormonal system involved in a myriad of cardiovascular functions. This system is composed of many different peptides that act in the heart through different receptors. One of the most important of these peptides is angiotensin II, which in pathological conditions triggers a set of actions that lead to heart failure. On the other hand, another RAS peptide, angiotensin-(1-7) is well known to develop powerful therapeutic effects in many forms of cardiac diseases. In the last decade, two new components of RAS were described, the heptapeptide alamandine and its receptor, the Mas-related G protein-coupled receptor member D (MrgD). Since then, great effort was made to characterize their physiological and pathological function in the heart. In this review, we summarize the latest insights about the actions of alamandine/MrgD axis in the heart, with particular emphasis in the cardiomyocyte. More specifically, we focused on their antihypertrophic and contractility effects, and the related molecular events activated in the cardiomyocyte.
Assuntos
Miócitos Cardíacos , Receptores Acoplados a Proteínas G , Miócitos Cardíacos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Sistema Renina-Angiotensina , Angiotensina II/metabolismo , Angiotensina I/metabolismo , Fragmentos de Peptídeos/metabolismoRESUMO
Diabetic cardiomyopathy (DC) describes diabetes-associated changes in the structure and function of myocardium that are not directly linked to other factors such as hypertension. Currently there are some models of DC; however, they take a large time period to mimic key features. In the present study, we investigated the effects of a short-term high-fat/high salt diet (HFHS) treatment on myocardial function and structure, and vascular reactivity in C57BL/6 male mice. After 14â¯weeks HFHS induced hypertension (MAPâ¯=â¯144.95⯱â¯16.13 vs 92.90⯱â¯18.95â¯mmâ¯Hg), low glucose tolerance (AUCâ¯=â¯1049.01⯱â¯74.79 vs 710.50⯱â¯52.57â¯a.u.), decreased insulin sensitivity (AUCâ¯=â¯429.83⯱â¯35.22 vs 313.67⯱â¯19.55â¯a.u.) and increased adiposity (epididymal fat weight 0.96⯱â¯0.10 vs 0.59⯱â¯0.06 OW/BWâ¯×â¯102), aspects present in metabolic syndrome. Cardiac evaluation showed diastolic dysfunction (E/A ratioâ¯=â¯1.20 vs 1.90â¯u.a.) and cardiomyocyte hypertrophy (cardiomyocyte areaâ¯=â¯502.82⯱â¯31.46 vs 385.58⯱â¯22.11⯵m2). Lastly, vascular reactivity was impaired with higher contractile response (136.10⯱â¯3.49 vs 120.37⯱â¯5.43%) and lower response to endothelium-dependent vasorelaxation (74.01⯱â¯4.35 vs 104.84⯱â¯3.57%). In addition, the diet was able to induce an inward coronary remodeling (vascular total area: SCNS 6185⯱â¯800.6 vs HFHS 4085⯱â¯213.7⯵m2). Therefore, we conclude that HFHS short-term treatment was able to induce metabolic syndrome-like state, cardiomyopathy and vascular injury working as an important tool to study cardiometabolic diseases.
Assuntos
Cardiomiopatias/etiologia , Dieta Hiperlipídica/efeitos adversos , Síndrome Metabólica/etiologia , Cloreto de Sódio na Dieta/toxicidade , Animais , Peso Corporal , Modelos Animais de Doenças , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
AIMS: The nonpeptide Ang-(1-7) analog, AVE 0991, is recognized as having beneficial cardiovascular effects similar to those induced by Ang-(1-7). In this study, we evaluated the effects of AVE 0991 on cardiovascular functions and on cardiac and renal remodeling in rats with 2K1C renovascular hypertension. MAIN METHODS: Fisher rats underwent surgery to induce 2K1C renovascular hypertension and were then treated with AVE 0991 (1 or 3mg/kg) for 28days. At the end of treatment, the blood pressure (BP), heart rate (HR), and baroreflex sensitivity were evaluated, in conscious animals. The rats were then euthanized and the heart and kidneys removed for subsequent histological analysis. KEY FINDINGS: Treatment with AVE 0991 in 2K1C rats restored the baroreflex sensitivity of both bradycardic and tachycardic components to levels comparable to those of normotensive SHAM rats. At a higher dose (3mg/kg), AVE 0991 was also anti-hypertensive in 2K1C rats. Furthermore, AVE 0991 reduced the heart weight, thickness of myocardial fibers, number of inflammatory cells, and area of collagen deposition in the hearts of 2K1C rats compared to SHAM rats. The inflammatory process and tissue area of collagen deposition were decreased in the clipped kidney of AVE 0091-treated 2K1C rats. SIGNIFICANCE: Our data showed that oral treatment with AVE 0991 reduces blood-pressure cardiac remodeling and improves baroreflex sensitivity in 2K1C renovascular hypertensive rats.
Assuntos
Angiotensina I/química , Anti-Hipertensivos/uso terapêutico , Barorreflexo/efeitos dos fármacos , Hipertensão Renovascular/tratamento farmacológico , Imidazóis/uso terapêutico , Fragmentos de Peptídeos/química , Remodelação Ventricular/efeitos dos fármacos , Animais , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Colágeno/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Hipertensão Renovascular/metabolismo , Hipertensão Renovascular/patologia , Hipertensão Renovascular/fisiopatologia , Imidazóis/administração & dosagem , Imidazóis/química , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Ratos Endogâmicos F344RESUMO
BACKGROUND AND OBJECTIVE: It has been shown that the circulating Renin-Angiotensin System (RAS) is activated during normal pregnancy, but little is known about RAS in pregnancies complicated by gestational diabetes (GDM). GDM is considered not merely a temporary condition, but a harbinger of hypertension and type 2 diabetes. The aim of this study was to evaluate the circulating RAS profile in normotensive women with GDM at the third trimester of pregnancy and to compare the results with healthy pregnant and non-pregnant age-matched women. METHODS: The diagnostic criteria for GDM followed the recommendations of the American Diabetes Association. Angiotensin I (Ang I), Angiotensin II (Ang II) and Angiotensin 1-7 [Ang-(1-7)] were determined in 24 pregnant patients with GDM; 12 healthy pregnant women and 12 non-pregnant women by radioimmunoassay. RESULTS: Levels of Ang I, Ang II and Ang-(1-7) were higher in pregnant women (p<0.05), but showed a different pattern in the GDM group, in which reduced Ang-(1-7) circulating levels were found (p<0.05). This observation was confirmed by the significantly lower Ang-(1-7)/Ang I ratio (p<0.05). CONCLUSION: Our data suggest that reduced levels of the vasodilator Ang-(1-7) could be implicated in the endothelial dysfunction seen in gestational diabetic women during and after pregnancy.