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1.
Peptides ; 87: 41-49, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27884622

RESUMO

The renin-angiotensin-system is an important component of cardiovascular control and is up-regulated under various conditions, including hypertension and menopause. The aim of this study was to evaluate the effects of swimming training and estrogen therapy (ET) on angiotensin-II (ANG II)-induced vasoconstriction and angiotensin-(1-7) [ANG-(1-7)]-induced vasorelaxation in aortic rings from ovariectomized spontaneously hypertensive rats. Animals were divided into Sham (SH), Ovariectomized (OVX), Ovariectomized treated with E2 (OE2), Ovariectomized plus swimming (OSW) and Ovariectomized treated with E2 plus swimming (OE2+SW) groups. ET entailed the administration of 5µg of 17ß-Estradiol three times per week. Swimming was undertaken for sixty minutes each day, five times per week. Both, training and ET were initiated seven days following ovariectomy. Forty-eight hours after the last treatment or training session, the animals' systolic blood pressures were measured, and blood samples were collected to measure plasma ANG II and ANG-(1-7) levels via radioimmunoassay. In aortic rings, the vascular reactivity to ANG II and ANG-(1-7) was assessed. Expression of ANG-(1-7) in aortic wall was analyzed by immunohistochemistry. The results showed that both exercise and ET increased plasma ANG II levels despite attenuating systolic blood pressure. Ovariectomy increased constrictor responses to ANG II and decreased dilatory responses to ANG-(1-7), which were reversed by swimming independently of ET. Moreover, it was observed an apparent increase in ANG-(1-7) content in the aorta of the groups subjected to training and ET. Exercise training may play a cardioprotective role independently of ET and may be an alternative to ET in hypertensive postmenopausal women.


Assuntos
Aorta/metabolismo , Terapia por Exercício , Hipertensão/terapia , Condicionamento Físico Animal , Angiotensina I/sangue , Angiotensina II/sangue , Animais , Aorta/patologia , Estradiol/administração & dosagem , Estrogênios/metabolismo , Estrogênios/uso terapêutico , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Ovariectomia , Fragmentos de Peptídeos/sangue , Ratos , Ratos Endogâmicos SHR , Sistema Renina-Angiotensina/genética
2.
Curr Opin Nephrol Hypertens ; 26(1): 36-42, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27798458

RESUMO

PURPOSE OF REVIEW: Angiotensin II is a main regulator of kidney function. Renal actions mediated by the angiotensin AT1 receptor have been well known for many years. In contrast, several details of angiotensin AT2 receptor actions in kidney physiology and pathophysiology were only described very recently. These findings are reviewed in this article. RECENT FINDINGS: Regarding the role of the angiotensin AT2 receptor in kidney physiology, a major recent finding was that the AT2 receptor-mediated inhibition of Na-H exchanger-3 and Na/K-ATPase in the renal proximal tubules is caused by internalisation of these transporters, thus reducing reabsorption and increasing natriuresis/diuresis. Regarding renal pathology, several studies demonstrated an attenuation of renal injury caused by diabetes or by obesity with or without high-salt diet through anti-inflammatory, antifibrotic, and antioxidative mechanisms. Generally, AT2 receptor expression seems increased and AT2 receptor-mediated effects stronger in female and obese animals. SUMMARY: The recent findings about the role of the angiotensin AT2 receptor in renal health and disease strongly suggest that pharmacological targeting of this receptor with selective agonists is a promising therapeutic strategy for inducing diuresis/natriuresis (also additive to established diuretics) and for the treatment of diabetic nephropathy or kidney disease of other pathogenesis.


Assuntos
Nefropatias Diabéticas/metabolismo , Túbulos Renais Proximais/metabolismo , Obesidade/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Animais , Nefropatias Diabéticas/tratamento farmacológico , Diurese , Humanos , Natriurese , Receptor Tipo 2 de Angiotensina/agonistas , Fatores Sexuais , Trocador 3 de Sódio-Hidrogênio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores
3.
J Proteome Res ; 11(6): 3370-81, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22497526

RESUMO

Angiotensin-(1-7) [Ang-(1-7)] is an endogenous ligand of the Mas receptor and induces vasodilation, positive regulation of insulin, and antiproliferative and antitumorigenic activities. However, little is known about the molecular mechanisms behind these biological properties. Aiming to identify proteins involved in the Ang-(1-7) signaling, we performed a mass spectrometry-based time-resolved quantitative phosphoproteome study of human aortic endothelial cells (HAEC) treated with Ang-(1-7). We identified 1288 unique phosphosites on 699 different proteins with 99% certainty of correct peptide identification and phosphorylation site localization. Of these, 121 sites on 79 proteins had their phosphorylation levels significantly changed by Ang-(1-7). Our data suggest that the antiproliferative activity of Ang-(1-7) is due to the activation or inactivation of several target phosphoproteins, such as forkhead box protein O1 (FOXO1), mitogen-activated protein kinase 1 (MAPK), proline-rich AKT1 substrate 1 (AKT1S1), among others. In addition, the antitumorigenic activity of Ang-(1-7) is at least partially due to FOXO1 activation, since we show that this transcriptional factor is activated and accumulated in the nucleus of A549 lung adenocarcinoma cells treated with Ang-(1-7). Moreover, Ang-(1-7) triggered changes in the phosphorylation status of several known downstream effectors of the insulin signaling, indicating an important role of Ang-(1-7) in glucose homeostasis. In summary, this study provides new concepts and new understanding of the Ang-(1-7) signal transduction, shedding light on the mechanisms underlying Mas activation.


Assuntos
Angiotensina I/fisiologia , Células Endoteliais/metabolismo , Fragmentos de Peptídeos/fisiologia , Fosfoproteínas/metabolismo , Processamento de Proteína Pós-Traducional , Transporte Ativo do Núcleo Celular , Aorta/citologia , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Humanos , Anotação de Sequência Molecular , Fosforilação , Mapas de Interação de Proteínas , Proteoma/metabolismo , Proteômica , Transdução de Sinais
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