Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.940
Filtrar
1.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(3): 219-222, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32164092

RESUMO

The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Inflamação , Peptidil Dipeptidase A , Pneumonia Viral/tratamento farmacológico , Sistema Renina-Angiotensina , Angiotensina II , Animais , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Pressão Sanguínea/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Pulmão , Fragmentos de Peptídeos , Peptidil Dipeptidase A/efeitos dos fármacos , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/etiologia , Prognóstico , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
2.
Braz J Cardiovasc Surg ; 34(5): 605-609, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31719011

RESUMO

Atrial fibrillation is a common type of arrhythmia and is an important cause of stroke and heart failure. vitamin D is an emerging risk factor of AF, and is implicated in the pathophysiology of atrial fibrillation. It has been established that this vitamin is extensively involved in the regulation of both the renin angiotensin aldosterone system and the immune system. Epidemiological studies have not yet reached a consensus on the possible association between vitamin D deficiency and atrial fibrillation. Better research designs and methods can further clarify the relationship between the two.


Assuntos
Fibrilação Atrial/etiologia , Fibrilação Atrial/metabolismo , Deficiência de Vitamina D/complicações , Humanos , Sistema Renina-Angiotensina/fisiologia , Fatores de Risco
3.
BMC Infect Dis ; 19(1): 866, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638922

RESUMO

BACKGROUND: Hand, foot and mouth disease (HFMD) remains a burdensome health issue in mainland China. Enterovirus71 (EV-A71) is the main pathogen of severe HFMD. Continuous hemofiltration improves fluid overload, restores kidney function and alleviates inflammatory reactions. The aim of the present study was to evaluate the effects of continuous veno-venous hemodiafiltration (CVVHDF) on severe HFMD caused by EV-A71(EV-A71-HFMD) in a pediatric intensive care unit (PICU). METHODS: A retrospective observational study was performed in a tertiary university PICU from January 2012 to December 2016. Children with severe EV-A71-HFMD complicated by cardiopulmonary failure were included. The patients were divided into a CVVHDF group and a conventional therapy (control) group (non-CVVHDF). The demographics, characteristics, and outcomes between the groups were collected and analyzed. RESULTS: Twenty-nine patients with severe EV-A71-HFMD were enrolled. The 28-day mortality was 17.6% (3/17) in the CVVHDF group and 33.3% (4/12) in the non-CVVHDF group, with no statistical significance between the two groups (P = 0.403). The median interval between CVVHDF initiation and PICU admission was 6 (4,8.5) hrs, and the median duration of CVVHDF was 48 (36, 64) hrs. The left ventricular ejection fraction (LVEF) and cardiac index (CI) in the CVVHDF group were improved after treatment. The plasma levels of catecholamines and renin-angiotensin-aldosterone system (RAAS) substances in the CVVHDF group were significantly decreased after treatment. The decreased catecholamines and RAAS substances included adrenalin (169.8 [145.5, 244.6] vs. 148.0 [109.0, 208.1] ng/L, P = 0.033), dopamine (152.7 [97.0, 191.1] vs. 96.0 [68.0, 160.9] ng/L, P = 0.026), angiotensin II (185.9 [125.2, 800.0] vs. 106.0 [90.8, 232.5] ng/L, P = 0.047), aldosterone (165.7 [94.0, 353.3] vs. 103.3 [84.3, 144.3] ng/L, P = 0.033), and renin (1.12 [0.74, 3.45] vs. 0.79 [0.52, 1.25] µg/L/h, P = 0.029), CONCLUSIONS: CVVHDF reduced the levels of catecholamines and RAAS substances and improved cardiovascular function. Continuous hemodiafiltration may represent a potential therapy in patients with severe EV-A71-HFMD complicated with cardiopulmonary failure.


Assuntos
Doenças Cardiovasculares/terapia , Enterovirus Humano A , Doença de Mão, Pé e Boca/terapia , Doença de Mão, Pé e Boca/virologia , Unidades de Terapia Intensiva Pediátrica , Doença Pulmonar Obstrutiva Crônica/terapia , Aldosterona/sangue , Angiotensina II/sangue , Doenças Cardiovasculares/complicações , Catecolaminas/sangue , Pré-Escolar , China , Feminino , Seguimentos , Doença de Mão, Pé e Boca/sangue , Doença de Mão, Pé e Boca/complicações , Hemodiafiltração/métodos , Humanos , Lactente , Masculino , Doença Pulmonar Obstrutiva Crônica/complicações , Renina/sangue , Sistema Renina-Angiotensina/fisiologia , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento
4.
Exp Eye Res ; 189: 107838, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31622617

RESUMO

As many other organs, the retina has a local renin-angiotensin-system (RAS). All main elements of the RAS are active in the retina: renin, angiotensinogen, angiotensin-converting enzymes. The functional role of the intraretinal RAS is not fully understood. So far, histological and functional analysis point to a regulation of ganglion cell activity and maybe also of bipolar cell activity, but it is not clear how RAS contributes to retinal signal processing. In contrast to local RAS in other organs, the retinal RAS is clearly separated from the systemic RAS. The angiotensin-2 (AngII)/AngI ratio in the retina is different to that in the plasma. However, it appears that the retinal pigment epithelium (RPE), that forms the outer blood/retina barrier, is a major regulator of the retinal RAS by producing renin. Interestingly, comparable to the kidney, the renin production in the RPE is under control of the angiotensin-2 receptor type-1 (AT1). AT1 localizes to the basolateral membrane of the RPE and faces the blood side of the blood/retina barrier. Increases in systemic AngII reduce renin production in the RPE and therefore decrease the intraretinal RAS activity. The relevance of the local RAS for retinal function remains unclear. Nevertheless, it is of fundamental significance to understand the pathology of systemically induced retinal diseases such as hypertension or diabetes.


Assuntos
Barreira Hematorretiniana/metabolismo , Sistema Renina-Angiotensina/fisiologia , Renina/biossíntese , Epitélio Pigmentado da Retina/metabolismo , Animais , Humanos
5.
Exp Eye Res ; 189: 107828, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31589840

RESUMO

Several lines of evidence support the existence of a renin-angiotensin system (RAS) in the retina that is separated from the blood stream by the retinal pigment epithelium (RPE). Under physiological conditions, increased activity of intraretinal RAS regulates neuronal activity of the retina but patho-physiologically participates in retinal degeneration such as hypertensive or diabetic retinopathy. Interestingly, the RPE appears to be a modulator of intraretinal RAS in response to changes in systemic RAS. As increased systemic RAS activity is associated with increased sympathetic tonus, we investigated whether systemic ß-adrenergic stimulation of the RPE also modulates renin expression in the RPE. In vivo, the mouse RPE expresses the ß-adrenergic receptor subtypes 1 and 2. Staining of retina sagittal sections showed tyrosine hydroxylase positive nerve endings in the choroid indicating adrenaline/noradrenaline production sites in close proximity to the RPE. Systemic infusion of isoproterenol increased renin expression in the RPE but not in the retina. This increase was sensitive to concomitant systemic application of the angiotensin-2 receptor-type-1 blocker losartan. In vitro analysis of renin gene expression using polarized porcine RPE showed that the activity of the renin promoter can be increased by cAMP stimulation (IBMX/forskolin) but was not influenced by angiotensin-2. Thus, with the identification of the ß-adrenergic system we added a new regulator of the retinal RAS with relevance for retinal function and pathology. Furthermore, it appears that the RPE is not only a close interaction partner of the photoreceptors but also a regulator or retinal activity in general.


Assuntos
Receptores Adrenérgicos beta/biossíntese , Sistema Renina-Angiotensina/fisiologia , Epitélio Pigmentado da Retina/metabolismo , Sistema Nervoso Simpático/fisiologia , Animais , Células Cultivadas , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Renina/biossíntese , Epitélio Pigmentado da Retina/citologia , Estimulação Química
6.
Endocr Regul ; 53(3): 178-186, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517631

RESUMO

OBJECTIVE: Epidemiological studies confirm that hypertensive patients respond differently to renin-angiotensin system (RAS) inhibition depending on their gender. The aim of present work is to focus on sex-dependent differences in RAS regulation under conditions of increased salt intake. METHOD: To investigate RAS, we measured the expression of angiotensinogen (Agt) mRNA, angiotensin receptor type 1 (AT1) mRNA and mitochondria assembly receptor (MasR) in the liver of rats under control conditions and after feeding with a salt diet (2% NaCl). In parallel, vascular endothelial growth factor A (VEGF-A) mRNA was analyzed. RESULTS: Regression analysis revealed sex-dependent differences in the correlation between mRNA expression of AT1 and that of Agt, MasR and VEGF-A in both groups. There was a significant negative correlation between AT1 and Agt mRNA expression in the male control group, but this correlation disappeared in males exposed to a salt diet. In females, AT1 and Agt expression correlated only in the group exposed to the salt diet. In control males, there was a borderline trend to correlation between AT1 and MasR mRNA expression. The correlation between AT1 and VEGF-A mRNA expression was significant only in the control females, however, after exposure to a salt diet, this correlation diminished. CONCLUSIONS: We hypothesize that RAS components expression is compensated differently in males and females. The observed loss of compensatory relationships in RAS between AT1 and Agt and AT1 and MasR in male rats under a salt diet can contribute to the differences observed in human with hypertension associated with an unhealthy diet.


Assuntos
Plasticidade Celular/efeitos dos fármacos , Fígado/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Caracteres Sexuais , Cloreto de Sódio na Dieta/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Feminino , Fígado/fisiologia , Masculino , Ratos , Sistema Renina-Angiotensina/fisiologia , Cloreto de Sódio/farmacologia , Cloreto de Sódio na Dieta/farmacologia
7.
PLoS Comput Biol ; 15(9): e1007346, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31513566

RESUMO

We performed a mathematical analysis of the dynamic control loops regulating the vasomotor tone of vascular smooth muscle, blood volume, and mean arterial pressure, which involve the arginine vasopressin (AVP) system, the atrial natriuretic peptide system (ANP), and the renin-angiotensin-aldosterone system (RAAS). Our loop analysis of the AVP-ANP-RAAS system revealed the concurrent presence of two different regulatory mechanisms, which perform the same qualitative function: one affects blood pressure by regulating vasoconstriction, the other by regulating blood volume. Both the systems are candidate oscillators consisting of the negative-feedback loop of a monotone system: they admit a single equilibrium that can either be stable or give rise to oscillatory instability. Also a subsystem, which includes ANP and AVP stimulation of vascular smooth muscle cells, turns out to be a candidate oscillator composed of a monotone system with multiple negative feedback loops, and we show that its oscillatory potential is higher when the delays along all feedback loops are comparable. Our results give insight into the physiological mechanisms ruling long-term homeostasis of blood hydraulic parameters, which operate based on dynamical loops of interactions.


Assuntos
Pressão Sanguínea/fisiologia , Volume Sanguíneo/fisiologia , Homeostase/fisiologia , Modelos Biológicos , Arginina Vasopressina/metabolismo , Fator Natriurético Atrial/metabolismo , Cálcio/metabolismo , Biologia Computacional , Retroalimentação Fisiológica/fisiologia , Humanos , Músculo Liso Vascular/citologia , Sistema Renina-Angiotensina/fisiologia
8.
J Physiol Pharmacol ; 70(3)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31539880

RESUMO

The local renin-angiotensin-aldosterone system (RAAS) is fully expressed in the human skin at the mRNA and protein level. Local RAAS is known to play a regulatory function in epidermal proliferation, wound healing, scarring, cutaneous heating adaptation, and aging. There are also some indications of its role in the regulation of hair growth and sebum secretion. Impaired wound healing, skin diseases associated with diabetes, cancer development, psoriasis, and scleroderma may be related to changes in skin RAAS activity. Extensive research has shown that RAAS-modulating drugs can affect the skin when applied orally or topically, creating new therapeutic approaches against dermatological diseases.


Assuntos
Aldosterona/metabolismo , Sistema Renina-Angiotensina/fisiologia , Dermatopatias/fisiopatologia , Pele/fisiopatologia , Animais , Humanos , Fenômenos Fisiológicos da Pele
9.
Nutrients ; 11(9)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546789

RESUMO

The systemic renin-angiotensin system (RAS) is an important regulator of body fluid and sodium homeostasis. Angiotensin II (AngII) is a key active product of the RAS. We previously revealed that circulating AngII suppresses amiloride-sensitive salt taste responses and enhances the responses to sweet compounds via the AngII type 1 receptor (AT1) expressed in taste cells. However, the molecular mechanisms underlying the modulation of taste function by AngII remain uncharacterized. Here we examined the expression of three RAS components, namely renin, angiotensinogen, and angiotensin-converting enzyme-1 (ACE1), in mouse taste tissues. We found that all three RAS components were present in the taste buds of fungiform and circumvallate papillae and co-expressed with αENaC (epithelial sodium channel α-subunit, a salt taste receptor) or T1R3 (taste receptor type 1 member 3, a sweet taste receptor component). Water-deprived mice exhibited significantly increased levels of renin expression in taste cells (p < 0.05). These results indicate the existence of a local RAS in the taste organ and suggest that taste function may be regulated by both locally-produced and circulating AngII. Such integrated modulation of peripheral taste sensitivity by AngII may play an important role in sodium/calorie homeostasis.


Assuntos
Regulação da Expressão Gênica/fisiologia , Glutamato Descarboxilase/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Sistema Renina-Angiotensina/fisiologia , Paladar/fisiologia , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Animais , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Feminino , Glutamato Descarboxilase/genética , Proteínas de Fluorescência Verde , Masculino , Camundongos , Receptores Acoplados a Proteínas-G/genética , Renina/genética , Renina/metabolismo , Papilas Gustativas/química
10.
J Nippon Med Sch ; 86(4): 192-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31484880

RESUMO

Twin to twin transfusion syndrome (TTTS) is a major complication of monochorionic diamniotic (MD) twins, and its onset is known to be associated with placental vascular anastomoses and blood flow imbalance. In a typical case of TTTS, the recipient develops polyhydramnios, weight gain, cardiomegaly and hydrops fetalis in the uterus. In contrast, the donor develops oligohydramnios and intrauterine growth restriction. Recently, the significance of the renin-angiotensin-aldosterone system (RAAS) that transfers from the donor to the recipient has attracted interest in the fetal circulation of TTTS. The donor has decreased renal blood flow due to decreased circulating blood volume. For this reason, the secretion of RAAS hormones is augmented in the fetal kidneys of the donor. In TTTS, these RAAS hormones from the donor transfer to the recipient through the anastomosed vessels. In addition to excess preload, the recipient heart is exposed to excess afterload due to systemic vasoconstriction through RAAS hormones. Commonly occurring complications in the recipient include myocardial hypertrophy, atrioventricular valve regurgitation, and pulmonary valve stenosis or pulmonary atresia. Fetoscopic laser photocoagulation (FLP) has been introduced recently because neither mortality nor neurological morbidity have been satisfactorily improved with conventional treatment. FLP is a curative method that may improve the prognosis of TTTS. In Japan, this procedure has been performed frequently, and positive neurological outcomes have been achieved.


Assuntos
Transfusão Feto-Fetal , Feto/irrigação sanguínea , Volume Sanguíneo , Cardiomegalia/embriologia , Cardiomegalia/etiologia , Feminino , Doenças Fetais/etiologia , Doenças Fetais/fisiopatologia , Retardo do Crescimento Fetal/etiologia , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/etiologia , Transfusão Feto-Fetal/patologia , Transfusão Feto-Fetal/terapia , Fetoscopia , Humanos , Terapia com Luz de Baixa Intensidade , Poli-Hidrâmnios/etiologia , Gravidez , Prognóstico , Estenose da Valva Pulmonar/embriologia , Estenose da Valva Pulmonar/etiologia , Circulação Renal , Sistema Renina-Angiotensina/fisiologia
11.
Exp Eye Res ; 188: 107788, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31479654

RESUMO

Diabetic retinopathy (DR) and retinal vein occlusion (RVO) are the two most common retinal vascular diseases and are major causes of vision loss and blindness worldwide. Recent and ongoing development of medical therapies including anti-vascular endothelial growth factor and corticosteroid drugs for treatment of these diseases have greatly improved the care of afflicted patients. However, severe manifestations of retinal vascular disease result in persistent macular edema, progressive retinal ischemia and incomplete visual recovery. Additionally, choroidal vascular diseases including neovascular age-related macular degeneration (NVAMD) and central serous chorioretinopathy (CSCR) cause vision loss for which current treatments are incompletely effective in some cases and highly burdensome in others. In recent years, aldosterone has gained attention as a contributor to the various deleterious effects of retinal and choroidal vascular diseases via a variety of mechanisms in several retinal cell types. The following is a review of the role of aldosterone in retinal and choroidal vascular diseases as well as our current understanding of the mechanisms by which aldosterone mediates these effects.


Assuntos
Aldosterona/fisiologia , Doenças Retinianas/fisiopatologia , Vasos Retinianos/fisiopatologia , Doenças da Coroide/metabolismo , Doenças da Coroide/fisiopatologia , Artérias Ciliares/metabolismo , Artérias Ciliares/fisiopatologia , Humanos , Sistema Renina-Angiotensina/fisiologia , Retina/fisiologia , Doenças Retinianas/metabolismo , Vasos Retinianos/metabolismo
12.
Med Hypotheses ; 131: 109309, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443781

RESUMO

Stroke and traumatic brain injury (TBI) are significant clinical problems characterized by high rate of mortality and long-lasting disabilities, and an unmet need for new treatments. Current experimental stroke and TBI research are evolving to focus more on understanding the brain's self-protective mechanisms to meet the critical need of developing new therapies for these disorders. In this hypothesis-based manuscript, I provide several lines of evidence that peptidase neurolysin (Nln) is one of the brain's potent, self-protective mechanisms promoting preservation and recovery of the brain after acute injury. Based on published experimental observations and ongoing studies in our laboratory, I posit that Nln is a compensatory and cerebroprotective mechanism in the post-stroke/TBI brain that functions to process a diverse group of extracellular neuropeptides and by that to reduce excitotoxicity, oxidative stress, edema formation, blood brain barrier hyper-permeability, and neuroinflammation. If this hypothesis is correct, Nln could potentially serve as a single therapeutic target to modulate the function of multiple targets, the involved neuropeptide systems, critically involved in various mechanisms of brain injury and cerebroprotection/restoration. Such multi-pathway target would be highly desired for pharmacotherapy of stroke and TBI, because targeting one pathophysiological pathway has proven to be ineffective for such complex disorders.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Metaloendopeptidases/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neuropeptídeos/metabolismo , Acidente Vascular Cerebral/metabolismo , Doença Aguda , Animais , Lesões Encefálicas Traumáticas/fisiopatologia , Morte Celular , Hipóxia Celular , Células Cultivadas , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Terapia Genética , Humanos , Metaloendopeptidases/biossíntese , Metaloendopeptidases/genética , Camundongos , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Neurotoxinas/farmacologia , Bulbo Olfatório/metabolismo , Estresse Oxidativo , Oxigênio/farmacologia , Ratos , Proteínas Recombinantes/metabolismo , Sistema Renina-Angiotensina/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Regulação para Cima
13.
Exp Eye Res ; 187: 107770, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31449794

RESUMO

The renin-angiotensin system (RAS) plays a vital role in cardiovascular physiology and body homeostasis. In addition to circulating RAS, a local RAS exists in the retina. Dysfunction of local RAS, resulting in increased levels of Angiotensin II (Ang II) and activation of AT1R-mediated signaling pathways, contributes to tissue pathophysiology and end-organ damage. Activation of AT2R on other hand is known to counteract the effects of AT1R activation and produce anti-inflammatory and anti-oxidative effects. We examined the expression of angiotensin receptors in the retina by using transgenic dual reporter mice and by real-time RT-PCR. We further evaluated the effects of C21, a selective agonist of AT2R, in reducing Ang II, lipopolysaccharide (LPS) and hydrogen peroxide induced oxidative stress and inflammatory responses in cultured human ARPE-19 cells. We showed that both AT1Ra and AT2R positive cells are detected in different cell types of the eye, including the RPE/choroid complex, ciliary body/iris, and neural retina. AT1Ra is more abundantly expressed than AT2R in mouse retina, consistent with previous reports. In the neural retina, AT1Ra are also detected in photoreceptors whereas AT2R are mostly expressed in the inner retinal neurons and RGCs. In cultured human RPE cells, activation of AT2R with C21 significantly blocked Ang II, LPS and hydrogen peroxide -induced NF-κB activation and inflammatory cytokine expression; Ang II and hydrogen peroxide-induced reactive oxygen species (ROS) production and MG132-induced apoptosis, comparable to the effects of Angiotensin-(1-7) (Ang-(1-7)), another protective component of the RAS, although C21 is more potent in reducing some of the effects induced by Ang II, whereas Ang-(1-7) is more effective in reducing some of the LPS and hydrogen peroxide-induced effects. These results suggest that activation of AT2R may represent a new therapeutic approach for retinal diseases.


Assuntos
Receptor Tipo 2 de Angiotensina/metabolismo , Receptores de Angiotensina/agonistas , Epitélio Pigmentado da Retina/efeitos dos fármacos , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Sobrevivência Celular , Células Cultivadas , Citocinas/metabolismo , Regulação da Expressão Gênica/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , NF-kappa B/metabolismo , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptor Tipo 2 de Angiotensina/genética , Sistema Renina-Angiotensina/fisiologia , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia
15.
Exp Eye Res ; 187: 107766, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31425690

RESUMO

Angiotensin II and aldosterone are the main effectors of the renin-angiotensin aldosterone system (RAAS) and have a central role in hypertension as well as cardiovascular and renal disease. The localization of RAAS components within the retina has led to studies investigating the roles of angiotensin II, aldosterone and the counter regulatory arm of the pathway in vision-threatening retinopathies. This review will provide a brief overview of RAAS components as well as the vascular pathology that develops in the retinal diseases, retinopathy of prematurity, diabetic retinopathy and neovascular age-related macular degeneration. The review will discuss pre-clinical and clinical evidence that modulation of the RAAS alters the development of vasculopathy and inflammation in the aforementioned retinopathies, as well as the emerging role of aldosterone and the mineralocorticoid receptor in central serous chorioretinopathy.


Assuntos
Aldosterona/fisiologia , Angiotensina II/fisiologia , Retinopatia Diabética/fisiopatologia , Vasos Retinianos/fisiologia , Retinite/fisiopatologia , Retinopatia da Prematuridade/fisiopatologia , Degeneração Macular Exsudativa/fisiopatologia , Inibidores da Enzima Conversora de Angiotensina , Humanos , Receptor Tipo 1 de Angiotensina , Sistema Renina-Angiotensina/fisiologia
16.
Exp Eye Res ; 187: 107753, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31408629

RESUMO

The retina is known to have a local renin-angiotensin system (RAS) and dysfunction in the RAS is often associated with diseases of the retinal vasculature that cause irreversible vision loss. Regulation of the retinal vasculature to meet the metabolic needs of the tissues occurs through a mechanism called neurovascular coupling, which is critical for maintaining homeostatic function and support for neurons. Neurovascular coupling is the process by which support cells, including glia, regulate blood vessel calibre and blood flow in response to neural activity. In retinal vascular diseases, this coupling mechanism is often disrupted. However, the role that angiotensin II (Ang II), the main effector peptide of the RAS, has in regulating both the retinal vasculature and neurovascular coupling is not fully understood. As components of the RAS are located on the principal neurons, glia and blood vessels of the retina, it is possible that Ang II has a role in regulating communication and function between these three cell types, and therefore the capacity to regulate neurovascular coupling. This review focuses on components of the RAS located on the retinal neurovascular unit, and the potential of this system to contribute to blood flow modulation in the healthy and compromised retina.


Assuntos
Retinopatia Diabética/fisiopatologia , Microglia/fisiologia , Sistema Renina-Angiotensina/fisiologia , Vasos Retinianos/fisiologia , Angiotensina II/fisiologia , Animais , Humanos
17.
Plast Reconstr Surg ; 144(2): 372-384, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31348346

RESUMO

BACKGROUND: We investigated expression of prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 by the embryonic stem cell-like population on the endothelium of the microvessels and perivascular cells within keloid-associated lymphoid tissues. METHODS: Immunohistochemical staining for prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 was performed on 11 formalin-fixed, paraffin-embedded sections of keloid tissue samples. Immunofluorescence staining was performed on three keloid tissue samples by co-staining with OCT4, CD34, ERG, and tryptase. Real-time quantitative polymerase chain reaction was performed on five keloid tissue samples and four keloid-derived primary cell lines. Western blotting was performed on the four keloid-derived primary cell lines for mRNA and protein expression of these proteins, respectively. RESULTS: Immunohistochemical and immunofluorescence staining showed expression of prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 in all 11 keloid tissue samples. Prorenin receptor and angiotensin II receptor 1 were expressed on the endothelium and the pericyte layer of the microvessels and perivascular cells, angiotensin II receptor 2 was localized to the endothelium of the microvessels and the tryptase-positive perivascular cells, and angiotensin-converting enzyme was localized to the endothelium of the microvessel, within the keloid-associated lymphoid tissues. Real-time quantitative polymerase chain reaction showed transcripts of prorenin receptor, angiotensin-converting enzyme, and angiotensin II receptor 1 in the keloid tissue samples and keloid-derived primary cell lines, whereas angiotensin II receptor 2 was detected in keloid tissue samples only. Western blotting confirmed the presence of prorenin receptor, angiotensin-converting enzyme, and angiotensin II receptor 1 in the keloid-derived primary cell lines. CONCLUSION: Prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 were expressed by the embryonic stem cell-like population within the keloid-associated lymphoid tissues, suggesting that this primitive population may be a potential therapeutic target by modulation of the renin-angiotensin system.


Assuntos
Células-Tronco Embrionárias/metabolismo , Queloide/metabolismo , Sistema Renina-Angiotensina/fisiologia , Adolescente , Adulto , Antígenos CD34/metabolismo , Linhagem Celular , Criança , Pré-Escolar , Feminino , Imunofluorescência , Humanos , Queloide/patologia , Masculino , Pessoa de Meia-Idade , Fator 3 de Transcrição de Octâmero/metabolismo , Peptidil Dipeptidase A/metabolismo , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Receptores de Superfície Celular/metabolismo , Regulador Transcricional ERG/metabolismo , Adulto Jovem
18.
J Physiol Pharmacol ; 70(2)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31356181

RESUMO

Local renin-angiotensin systems (RAS) are found in many tissues. The main physiological effects of RAS are driven by the balance between two pathways: the angiotensin-converting enzyme I - angiotensin II receptor type 1 (ACE1-AT1R) axis and the angiotensin-converting enzyme 2 - Mas-receptor (ACE2-MAS) axis. The local intestinal RAS functions both as a paracrine regulator and as a regulator of inflammation. The expression of local RAS is known to change with age in many tissues, but age-related changes in the intestinal RAS have not been studied comprehensively. The present study characterized age-related changes in two main pathways of local RAS in the jejunum and colon of young and adult rats, in normotensive and hypertensive strains. The main finding was that 33-week-old rats exhibit an increased ratio of ACE1/ACE2 activities and protein quantity ratios compared to young rats. As the relationship of ACE1 and ACE2 mediated pathways drives the total physiological effects of RAS, the results indicate that the function of intestinal RAS changes with age. It is possible that age-related increase in ACE1-AT1R axis introduces more pro-inflammatory and fibrogenic conditions in the intestine.


Assuntos
Hipertensão/fisiopatologia , Intestinos/fisiologia , Sistema Renina-Angiotensina/fisiologia , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Animais , Pressão Sanguínea/fisiologia , Hipertensão/metabolismo , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Endogâmicos SHR , Receptor Tipo 1 de Angiotensina/metabolismo , Renina/metabolismo
19.
Rev Med Chil ; 147(4): 490-498, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344212

RESUMO

The renin-angiotensin-aldosterone system modulates volume, sodium and potassium homeostasis. In the setting of a high sodium diet, up to 30% of patients with hypertension have a low or suppressed renin and increased volume. This phenotype of low renin hypertension (LRH) is multifactorial and includes infrequent inherited genetic syndromes, milder phenotypes of classic diseases and environmental exposures. All these conditions have in common a higher cardiovascular risk mediated by the over activation of the mineralocorticoid receptor (MR), present not only in the kidney, but also in vasculature, myocardium and adipocytes. Consequently, the aim of LRH treatment goes beyond the control of blood pressure and requires antagonizing MR with specific pharmacologic agents, pursuing normalization of renin as a clinical objective. Due to the unusual evaluation of renin status by non-endocrinologists and lack of disease awareness, only a minority of hypertensive patients receive this pathophysiologically-driven treatment that should reduce cardiovascular outcomes.


Assuntos
Hipertensão/metabolismo , Hipertensão/terapia , Sistema Renina-Angiotensina/fisiologia , Aldosterona/metabolismo , Gerenciamento Clínico , Humanos , Hipertensão/fisiopatologia , Receptores de Mineralocorticoides/metabolismo , Renina/metabolismo
20.
Biol Sex Differ ; 10(1): 31, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262355

RESUMO

Obesity is a global epidemic that greatly increases risk for developing cardiovascular disease and type II diabetes. Sex differences in the obese phenotype are well established in experimental animal models and clinical populations. While having higher adiposity and obesity prevalence, females are generally protected from obesity-related metabolic and cardiovascular complications. This protection is, at least in part, attributed to sex differences in metabolic effects of hormonal mediators such as the renin-angiotensin system (RAS). Previous literature has predominantly focused on the vasoconstrictor arm of the RAS and shown that, in contrast to male rodent models of obesity and diabetes, females are protected from metabolic and cardiovascular derangements produced by angiotensinogen, renin, and angiotensin II. A vasodilator arm of the RAS has more recently emerged which includes angiotensin-(1-7), angiotensin-converting enzyme 2 (ACE2), mas receptors, and alamandine. While accumulating evidence suggests that activation of components of this counter-regulatory axis produces positive effects on glucose homeostasis, lipid metabolism, and energy balance in male animal models, female comparison studies and clinical data related to metabolic outcomes are lacking. This review will summarize current knowledge of sex differences in metabolic effects of the RAS, focusing on interactions with gonadal hormones and potential clinical implications.


Assuntos
Sistema Renina-Angiotensina/fisiologia , Caracteres Sexuais , Angiotensinas/metabolismo , Animais , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Receptores de Angiotensina/metabolismo , Renina/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA