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Item Tratamento com aceturato de diminazeno ou angiotensina-(1-7) em ratas hipertensas gestantes atenua disfunções cardiovasculares na prole(Universidade Federal de Goiás, 2019-04-22) Bessa, Amanda de Sá Martins de; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Castro, Carlos Henrique de; Costa, Renata Mazaro; Fonseca, Silvia Carolina GuatimosimIt has been proven that harmful stimuli during gestation can promote deleterious outcomes in offspring. Furthermore, previous studies have observed that the Renin-angiotensin system (RAS) can play a role in this pathological process. TheACE2/Ang-(1-7)/Mas axis presents several protective actions in the cardiovascular system. Thus, the aim of this study was to investigate whether the treatment with diminazene aceturate (DIZE), a putative ACE2 activator, or with Angiotensin-(1-7) during the pregnancy could attenuate the development of cardiovascular dysfunctions in the adult offspring of spontaneously hypertensive rats (SHR). For this, pregnant SHR received DIZE or Ang-(1-7) during the gestation. The SBP was measured in the male offspring by tail-cuff plethysmography. Thereafter, the left ventricular contractile function and coronary reactivity were evaluated by the Langendorff technique. Aortic vascular reactivity was also evaluated by isolated vessel in an organ bath. Samples of the LV were collected for histology and Western blot assay. Maternal treatment with DIZE (SHR: 181 ± 2.03 vs. SHR DIZE: 166.6 ± 0.35 mmHg, P <0.05) or Ang-(1-7) (SHR: 167.3 ± 1.79 vs. SHR Ang-(1-7): 153.8 ± 1.75 mmHg, P <0.05) during pregnancy attenuated the increase of the SBP in adult offspring. Additionally, the treatments reduced the cardiomyocyte diameter (SHR: 16.3 ± 0.11 vs. SHR DIZE: 12.9 ± 0.95 μm, P <0.05) (SHR: 16.6 ± 0.12 vs. SHR Ang-(1-7): 14 ± 0.10 μm, P <0.05) and degradation of the extracellular matrix (SHR: 15.6 ± 0.96 vs. SHR DIZE: 9.0 ± 0.61%, P <0.05) (SHR: 17.2 ± 1.27 vs. SHR Ang- (1-7): 10.3 ± 0,73%, P <0.05) in LV. The maternal treatment with DIZE and Ang-(1-7) improved the coronary vasodilation induced by bradykinin in isolated hearts. The expressions of AT1, Mas, ACE, ACE2, ERK Total, P-ERK, TNF-α, Collagen I, SOD, and Catalase in LV were not modified with Ang-(1-7), but this treatment decreased the AT2 (SHR: 0.90 ± 0.03 vs. SHR Ang- (1-7): 0.74 ± 0.05, P <0.05) expression. These data show that the treatment with DIZE or Ang-(1-7) during gestation promoted beneficial effects in attenuating hypertension and cardiac remodeling in adult offspring.Item Efeito do peptídeo Bj-PRO-7a no remodelamento cardíaco em ratos hipertensos(Universidade Federal de Goiás, 2018-04-27) Jesus, Érika Fernandes de; Ianzer, Danielle Alves; http://lattes.cnpq.br/7609262674053858; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Ianzer, Danielle Alves; http://lattes.cnpq.br/7609262674053858; Ferreira, Anderson José; Biancardi, Manoel FranciscoBj-PRO-7a, a proline-rich oligopeptide isolated from Bothrops jararaca snake venom, was able to reduce blood pressure and heart rate in hypertensive animals. However, it is not yet known whether this peptide may have beneficial effects on cardiac remodeling. Herein, we evaluate the effect of the Bj-PRO-7a in spontaneously hypertensive rats. Normotensive (Wistar) and spontaneously hypertensive (SHR) rats were divided into 3 groups: 1) Wistar treated with 0.9% saline, s.c.; 2) SHR treated with 0.9% saline, s.c.; and 3) SHR treated with BjPRO-7a (71 nmol/Kg/day, s.c.). The animals were treated during 28 days. The systolic blood pressure was weekly measured by tail-cuff plethysmography. At the end of the treatment, cardiac function was evaluated in isolated perfused heart preparation. The ventricular mass index was calculated by the ratio between the left ventricular weight and tibia length. The cardiomyocyte diameter and interstitial and perivascular fibrosis of the left ventricle were evaluated using the Picrossirius staining. The detection of collagen III deposition was evaluated by immunofluorescence. Fibroblast proliferation were assessed by immunohistochemistry to detect proliferating cell nuclear antigen (PCNA). The expression of catalase, SOD and ERK1/2, MMP-2 and MMP-9 was assessed by Western Blot. In our protocol, the Bj-PRO-7a was unable to reduce the systolic blood pressure of the SHRs. However, this peptide attenuated the development of the cardiomyocyte hypertrophy in these animals. Additionally, the deposition of the interstitial and perivascular fibrosis in SHR was significantly reduced by the treatment with Bj-PRO-7a. This peptide did not alter the collagen III deposition in hypertensive rat hearts. The Bj-PRO-7a reduced positive PCNA-labeled fibroblasts. The expression of catalase, SOD and ERK1/2 was significantly increased in SHR, but the Bj-PRO-7a attenuates this increase. The expression of MMP-2 and MMP-9 was not different in SHR hearts, but the Bj-PRO-7a increased the expression of the MMP-2 in the heart of these animals. Our findings demonstrate that the Bj-PRO-7a reduced the pathological cardiac remodeling through mechanism mediated by inhibition of the ERK1/2 and increasing MMP-2 expression. This data suggest that the Bj- xxiii PRO-7a could have a potential therapeutic for the treatment of cardiac diseases.Item Avaliação dos efeitos cardiovasculares do aceturato de diminazeno (DIZE) em ratos submetidos à sobrecarga pressórica(Universidade Federal de Goiás, 2014-02-12) Macedo, Larissa Matuda; Colugnati, Diego Basile; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314Activation of the Angiotensin Converting Enzyme 2 (ACE2)-Angiotensin-(1-7) [Ang(1-7)]-Mas Receptor axis results in protective effects in the cardiovascular system. ACE 2 is an important component of Renin-Angiotensin System, because it is able to convert Angiotensin II in Ang-(1-7). Recents studies have shown that diminazene aceturate (DIZE) act as an activator of ACE 2. The objective of this study was to evaluate the cardiovascular effects of chronic treatment with DIZE in pressureoverloaded rats and the possible mechanisms involved in these effects. Male Wistar rats (200-350 g) were divided in four groups: (1) Sham; (2) Coarcted (abdominal aortic banding, CAA); (3) CAA + DIZE (1 mg/kg, gavage); e (4) CAA + DIZE (1 mg/kg, gavage) + A-779 (120 µg/day, osmotic mini-pumps). Twenty one days after surgery procedure, the blood pressure was recorded, the hearts were isolated and perfused according to Langendorff method. Vascular reactivity was measured by isolated aortic ring preparation. In order to evaluate the cardiac hypertrophy, the left ventricular mass index (VMI) was calculated through the ratio of the left ventricular wet weight to tibia length. The cross-sectional area of cardiomyocytes (CSA) was also evaluated. The mRNA levels for ANP, BNP e TGF-β were also evaluated by qRT-PCR. The expression of ACE-2 and ERK1/2, AKT, mTOR, GATA-4, catalase and SOD proteins involved in hypertrophic pathways was analyzed by Western Blot technique. The results are presented as means ± SEM. One-way ANOVA followed by the Newman-Keuls post-test was used to analyze the blood pressure, cardiac morphometric parameters, isolated heart, qRT-PCR and Western Blot experiments. Two-way ANOVA followed by the Bonferroni post-test was used for aortic rings preparation protocols. All statistical analyses were considered significant at P<0.05. Isolated hearts from coarcted rats presented a significant decrease in the left ventricular end systolic pressure (128.1 ± 9.0 vs. 79.1 ± 12.8 mmHg in CAA, P<0.05), left ventricular developed pressure (118.1 ± 8.9 vs. 69.0 ± 12.7 mmHg in CAA, P<0.05), +dP/dt (2295.0 ± 161.8 vs. 1406.0 ± 246.5 mmHg/s in CAA, P<0.05) and dP/dt (1787.0 ± 166.0 vs. 1066.0 ± 181.9 mmHg/s in CAA, P<0.05). The DIZE treatment attenuated all of these effects induced by CAA. Moreover, DIZE treatment increased the coronary flow in hypertrophic hearts (CAA: 11.6 ± 0.8 vs. CAA+DIZE: 15.8 ± 0.6 mL/min, P<0.05). This effect was blocked by A-779. Pressure–overloaded hearts showed a significant increase in VMI (0.17 ± 0.01 vs. 0.21 ± 0.01 g/cm in CAA, P<0.05) and CSA (8.98 ± 0.54 vs. 10.72 ± 0.27 µm in CAA, P<0.05). The chronic treatment with DIZE prevented the heart hypertrophy (10.72 ± 0.27 in CAA vs. 9.25 ± 0.23 µm in CAA+DIZE, P<0.05). Indeed, treatment with A-779 attenuated the antihypertrophic effect induced by DIZE treatment. The coarcted rats presented a increase in mRNA expression of ANP, BNP and TGF-β and the DIZE treatment reverted this effect. The pressure overload decreased the acetylcholine-induced relaxation in aortic rings from coarcted rats and treatment with DIZE was not able to improve this effect. The coarctation decreased the phosphorylation of the AKT, which was not changed by DIZE treatment. The expression of ACE 2, total and phosphorylated ERK1/2, total AKT, mTOR, SOD and catalase was not changed by coarctation or by ACE 2 activation. These results show that the chronic treatment with DIZE was efficient in preventing the left ventricular hypertrophy and cardiac dysfunction induced by pressure overload. These effects were independent of changes in the expression of ACE 2, ERK1/2, AKT, mTOR, SOD and catalase. Thus, DIZE has important therapeutic potential for cardiovascular diseases.Item Avaliação da ação de nanopartículas magnéticas na função cardiovascular de ratos(Universidade Federal de Goiás, 2014-02-27) Nunes, Allancer Divino de Carvalho; Bakuzis, Andris Figueiroa; http://lattes.cnpq.br/3477269475651042; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Castro, Carlos Henrique de; Bakuzis, Andris Figueiroa; Colugnati, Diego Basile; Borges, Clayton LuizMagnetic Nanoparticles (MNPs) have been used for various biomedical applications. Importantly, manganese ferrite-based nanoparticles have a useful magnetic resonance imaging characteristics and potential for magnetic hyperthermia treatment, but their effects in the cardiovascular system are poorly reported. Thus, the objectives of this study were to determine the cardiovascular effects of four different types of manganese ferrite-based nanoparticles: albumin-coated (MnFe2O4 Albumin); citrate-coated (MnFe2O4 Citrate); tripolyphosphate-coated (MnFe2O4 Phosphate); and bare nanoparticles (MnFe2O4 Ionic). The direct effects of the MNPs on cardiac contractility were evaluated in isolated perfused rat hearts. The MnFe2O4 Citrate, but not MnFe2O4 Phosphate and MnFe2O4 Ionic induced a transient decreased in the Left Ventricular End Systolic Pressure. The MnFe2O4 Phosphate and MnFe2O4 Ionic, but not MnFe2O4 Citrate induced an increase in Left Ventricular End Diastolic Pressure which resulted decrease in a Left Ventricular End Developed Pressure. Indeed, MnFe2O4 Phosphate and MnFe2O4 Ionic also caused a decrease in the maximum dP/dt and minimum dP/dt. The three MNPs studied induced an increase in the perfusion pressure of isolated hearts. It is important to note that the ionic nanoparticle induced more significant changes in cardiac function. Interestingly, coating the bare nanoparticles with albumin reverted the MnFe2O4 Ionic-induced cardiac effects. MnFe2O4 Ionic, but not MnFe2O4 Phosphate or MnFe2O4 Citratre, induced a slight vasorelaxant effect in the isolated aortic rings. None of the MNPs were able to change heart rate or arterial blood pressure in conscious rats. In summary, the responses on ventricular function were found to be strongly dependent upon the surface nanoparticles coating layer. Also, although the MNPs were able to induce effects ex vivo, no significant changes were observed in vivo. Thus, given the proper dosages, these MNPs should be considered for possible therapeutic applications.Item Efeitos da Angiotensina-(1-7) e Angiotensina II no inotropismo cardíaco e vasomotricidade coronariana: um complexo envolvimento entre os receptores angiotensinérgicos(Universidade Federal de Goiás, 2018-04-26) Nunes, Allancer Divino de Carvalho; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Castro, Carlos Henrique de; Pedrino, Gustavo Rodrigues; Pansani, Aline; Bendhack, Lusiane Maria; Ferreira, Anderson JoséDespite Angiotensin-(1-7) [Ang-(1-7)] and Angiotensin II (Ang II) be considered important regulators of the cardiovascular system, its direct effects on cardiac contractility remain unclear and even controversial. Several studies, using different preparations, have showed that Ang-(1-7) or Ang II produce positive, negative or no inotropic effects. Thus, the aim of this study was to increase the knowledge about the effect of the low concentration of Ang-(1-7) and Ang II on cardiac contractility, coronary vascular function and the possible receptors and mechanisms of action involved in these effects. The in vivo effects of Ang-(1-7) and Ang II on cardiac contractility were evaluated in anesthetized rats. The Ang-(1-7) 4 nmol/L and Ang II 40 nmol/L caused negative inotropism in anesthetized rats. None of the peptides were able to change heart rate or arterial blood pressure in anesthetized rats. The direct effects of the Ang-(1-7) and Ang II on cardiac contractility were evaluated in isolated perfused rat hearts. After a basal period (30-40 minutes), the hearts were perfused for an additional 15 min with Ang-(1-7) and Ang II (20 pmol/L) in presence or absence of Mas receptor antagonist A-779 (2 nmol/L), AT2 receptor antagonist PD1233190 (2 nmol/L), AT1 receptor antagonist Losartan (1μmol/L), MrgD receptor antagonist D-PRO (2 nmol/L), ACE2 inhibitor DX600 (2nmol/L), Nitric Oxide synthase (NOS) inhibitor L-Name (10 nmol/L), Guanylyl cyclase (GC) inhibitor ODQ (200 nmol/L) and Adenylyl cyclase (AC) inhibitor MDL 12,330A (1μmol/L). Low concentrations of Ang-(1-7) and Ang II reduced the left ventricular end-systolic pressure (LVESP). The A-779 did not blocked the effect of Ang-(1-7) or Ang II. PD123319 and Losartan inhibited the Ang-(1-7) but not Ang II-induced negative inotropic effects. On the other hand, D-PRO was able to block the negative inotropic effect of the Ang II and Ang-(1-7). Furthermore, L-Name, ODQ and MDL 12,330A inhibited the Ang-(1-7) but not Ang II-induced negative inotropic effects. Similarly, low concentrations of Ang- (1-7) and Ang II-induced coronary vasodilatation. The A-779, D-PRO, L-Name, MDL 12,330A blocked the effect of Ang-(1-7) or Ang II. The DX600 blocked the vasodilatation induced by Ang II. PD123319, Losartan and ODQ inhibited the Ang-(1-7) but not Ang II-induced coronary vasodilatation. In addiction, the pharmacological blocked and gene silencing of AT1 receptor in endothelial human cells stimulated with Ang-(1-7) decreased AKT phosphorilation induced by Ang-(1-7). These data demonstrate that Ang-(1-7) and Ang II, at picomolar concentrations, induce significant and similar negative inotropic and coronary vasodilatation effects involving complex interaction mechanisms between many different receptors, altering intracellular signaling and their constitutive activity.Item Influência da Angiotensina-(1-7) na sensibilidade colinérgica cardíaca de ratos normotensos e hipertensos(Universidade Federal de Goiás, 2018-03-02) Pontes, Carolina Nobre Ribeiro; Custódio, Carlos Henrique Xavier; http://lattes.cnpq.br/0207928273284808; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Pansani, Aline Priscila; Pedrino, Gustavo Rodrigues; Castro, Carlos Henrique de; Custódio, Carlos Henrique XavierPrevious studies suggested that the Angiotensin-(1-7) [(Ang-(1-7)] is able to modulate the cardiac sympathetic control and beta-adrenergic sensitivity. However, whether or not Ang-(1- 7) modulates the cholinergic activity in the heart remains unknown. The aim of this study was to evaluate the influence of Ang-(1-7) upon cholinergic sensitivity of hearts from normotensive and hypertensive rats. Wistar and Spontaneously Hypertensive Rats (SHR) were anesthetized with urethane and underwent catheterization of femoral artery and left ventricle to record the arterial and intraventricular pressure, respectively. Following, a dose-response curve of acetylcholine (ACh, 10, 20, 40 and 80 ng/Kg, i.v. into femoral vein) was performed in the absence or presence of Ang-(1-7) (7 x 10-12 mol/min), Mas receptor antagonist A-779 (7 x 10-11 mol/min) or Ang-(1-7)+A-779. Isolated hearts were perfused according to the Langendorff technique. Increasing concentrations of ACh (10-7 to 10-5 mol/L) were added to the hearts in absence or presence of Ang-(1-7), (2 x 10-11 mol/L), A-779, (2 x 10-10 mol/L), Ang-(1-7)+A-779, MrgD receptor antagonist, D-PRO (2 x 10-10 mol/L) or D-PRO+Ang-(1-7). ACh-induced vasorelaxation was assessed in absence or presence of Ang-(1-7) (2 x 10-11 mol/L or 2 x 10-10 mol/L). Ang-(1-7) attenuated the effect of ACh in decreasing the intraventricular systolic, dP/dt max and dP/dt min in anesthetized Wistar and SHR. These effects were blocked by A-779. Ang-(1-7) did not change the amplitude of the hypotensive effect evoked by ACh in Wistar or SHRs. In isolated hearts, Ang-(1-7) also attenuated the reduction of the intraventricular systolic pressure, dP/dt max and dP/dt min evoked by ACh. A-779 blocked the Ang-(1-7) effects in hearts from Wistar. A-779 or D-PRO did not modify the effects of Ang-(1-7) in hearts from SHR, but in presence of D-PRO, Ang-(1-7) effects were equipotent. Ang-(1-7) attenuated the vasorelaxation induced by ACh in aorta from SHR by only in SHR group. These data suggest that Ang-(1-7) exerts differential modulation of cardiac cholinergic sensitivity during experimental primary hypertension, which is independent on blood pressure.Item Receptor Mas contribui para o desenvolvimento do remodelamento cardíaco(Universidade Federal de Goiás, 2016-03-21) Silva, Cintia do Carmo e; Costa, Renata Mazaro e; http://lattes.cnpq.br/5625298314637434; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Castro, Carlos Henrique dePrevious studies have demonstrated a protective effect of the Ang-(1-7)/Mas receptor axis on pathological cardiac hypertrophy. Also, the involvement of Mas receptor in the exercise-induced cardiac hypertrophy has been suggested. However, the role of the Ang-(1-7)/Mas receptor on pregnancy-induced cardiac remodeling remains unknown. Thus, the aim of this study was to evaluate the participation of the Mas receptor in the development of pregnancy and hypertrophy, fibrosis and cardiac function during pregnancy. Female Wistar rats were randomly shared in 3 groups: control (W-NP), pregnant (W-P), and pregnant treated with A-779 (W-P + A-779). Wild type and Masknockout mice were distributed in non-pregnant (WT and KO) and pregnant (WT-P and KO-P) groups. Gestational parameters such as, maternal weight, placental weight, fetus weight, fetus/placenta ratio, fertility, Loss pre embryonic, Loss pos embryonic were evaluated. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography. The medial part of the left ventricle (LV) was collected for cardiomyocytes morphometry analysis and extracellular matrix proteins deposition. Echocardiographic analysis was used to evaluate the cardiac function. Mas receptor blockade or genetic deletion of Mas did not alter the fertility or embryonic and fetal development. However, the Mas receptor antagonist decreased placental weight and increased fetus placenta ratio in rats. The pregnant KO mice presented a decreased maternal and fetal weight and increased fetus/placenta ratio. SBP was not changed by pregnancy or A-779 treatment in the Wistar rats. Pharmacological blockade or genetic deletion of Mas receptor attenuates the pregnancy-induced myocyte hypertrophy. The A-779 treatment or genetic deletion of the Mas receptor increased the collagen III deposition in LV from pregnant animals. KO mice presented a lower ejection fraction, fraction shortening, stroke volume and higher end systolic volume compared to WT. Interestingly, the pregnancy restored these parameters. In conclusion, these data show that Mas receptor can alter gestational and maternal parameters, and this is involved in the cardiomyocyte hypertrophy and in the control of the collagen III deposition in pregnancy condition. These alterations are associated with improvement of the cardiac function through Mas-independent mechanism.Item Avaliação de fármacos anti-hipertensivos na resposta vascular da Angiotensina-(1-7) em ratos submetidos à sobrecarga pressórica(Universidade Federal de Goiás, 2014-09-12) Souza, Álvaro Paulo Silva; Mendes, Elizabeth Pereira; http://lattes.cnpq.br/4901673689321551; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314; Castro, Carlos Henrique de; Mendes , Elizabeth Pereira; Ghedini, Paulo Cesar; Rabelo, Luisa AntasAccording to the World Health Organization (2013),cardiovascular diseases(CVD) are the major causes of death world wide. High blood pressure is the main risk factors for these diseases. The Renin-angiotensin System (RAS) is a important regulator of the cardiovascular functions. Among the components of the RAS, we can highlight the Angiotensin-(1-7) [Ang (1-7)]. It is known that the vasodilator effect of Ang-(1-7) is endothelium-dependent. Hypertension cause changes in the vascular structure and function, especially in the endothelium cells, leading to endothelial dysfunction and, consequently, impairment in the vasodilator effect of Ang (1-7). However, it has been shown that some classes of antihypertensive drugs (Angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors and Calcium channel blocker) improve the endothelial function. However, it is unknown if these drugs are able to improve the vasorelaxant effect of Ang-(1-7) in pressure-overload condition. Since several studies have pointed to Ang-(1-7)/Mas axis as a therapeutic potential for cardiovascular disease, is very important to understand the influence of the anti hypertensive drugs on the vascular effects of Ang-(1-7). Thus, the purpose of this study was to evaluate the influence of anti hypertensive drugs on the vascular effects of Angiotensin-(1-7) in pressure-overload rats. Wistar rats were submitted to abdominal aorta coarctation (ACo). Sham surgery was performed in the controls group. After 21 days of coarctation, blood pressure (BP) was recorded by carotid artery catheterization. Subsequently,the vasorelaxant effect of Ang-(1-7) were evaluated in aortic rings with or without acute pre-treatment (in vitro) of losartan 1µmol/L, captopril 1µmol/L or amlodipine 1µmol/L. To evaluate the effect of chronic treatment (in vivo), the ACo animals received the following treatments after surgery procedure: losartan 1 or 5 mg/kg/day, captopril 1 or 5 mg/kg/day, amlodipine 1 or 5 mg/kg/day, or DIZE 1 or 5 mg/kg/day. At the end of treatment, the aortic rings were isolated and the vasorrelaxant effect of Ang-(1-7) was evaluated. The increase of the BP was confirmed in the ACo rats. None of the treatment was able to reduce the blood pressure in ACo rats. Pressure overload decreased the relaxation induced by Ang (1-7) in isolated aortic rings. The in vitro pre treatment with losartan, captopril or amlodipine restored the vasorelaxant effect promoted by Ang-(1-7).A-779 or L-NAME blunted the vasorelaxant effect of Ang-(1-7) in aortic rings from CoA rats in presence of losartan.The in vivo treatment with losartan 1 mg/kg/day, captopril 1 mg/kg/day, amlodipine 1 mg/kg/day or DIZE 1 and 5 mg/kg/day was not effective in improving the vasorelaxant effect of Ang (1-7) in CoA aortic rings. However, losartan 5 mg/kg/day, captopril 5 mg/kg/day or amlodipine 5 mg/kg/Day improved the vasorelaxant effect of Ang-(1-7) in aortic rings from CoA rats. These results demonstrate that treatment in vitro or in vivo with some antihypertensive drugs (losartan, captopril and amlodipine) was able to improve the vasorelaxation effect of Ang (1-7) in the aorta from pressure-overloaded animals through mechanisms independent of blood pressure reduction. Therefore, the use of Ang-(1-7) associated with sub-pressor doses of antihypertensive agents may be a new therapeutic tool for the hypertension treatment.