RESUMO
The role of Renin-Angiotensin-System (RAS) in the pathogenesis of preeclampsia and eclampsia is still unclear. Our aim was to investigate plasma angiotensin II concentration [Ang II] in women with normotensive pregnancies (NP, n = 22) and severe preeclampsia in use of magnesium sulfate (SPE, n = 29). Despite no difference between the groups (SPE: 47.8 pg/ml vs NP: 39.7 pg/ml, p = 0.195), lower maternal age (p = 0.007) and primigravida (p = 0.028) were associated with lower [Ang II]. Plasma [Ang II] increased over the 24 h of magnesium sulfate administration (r = 0.48, p = 0.009). Our findings suggest that RAS may be involved with the mechanism of magnesium protection against eclamptic seizure.
Assuntos
Angiotensina II/efeitos dos fármacos , Sulfato de Magnésio/farmacologia , Pré-Eclâmpsia/tratamento farmacológico , Fatores Etários , Angiotensina II/sangue , Estudos de Casos e Controles , Feminino , Humanos , Sulfato de Magnésio/administração & dosagem , Pré-Eclâmpsia/sangue , Gravidez , Convulsões/prevenção & controleRESUMO
We studied Ang II receptor localization in different nuclei of the auditory system, by means of binding autoradiography, during brain development. The inferior colliculus (IC), a large midbrain structure which serves as an obligatory synaptic station in both the ascending and descending auditory pathways, exhibited high Ang II AT2 binding at all ages (P0, P8, P15, P30), being maximal at P15. These observations were confirmed by in situ hybridization and immunofluorescence at P15, demonstrating that AT2 receptor mRNA localized at the same area recognized by AT2 antibodies and anti ß III-tubulin suggesting the neuronal nature of the reactive cells. Ang II AT1 receptors were absent at early developmental ages (P0) in all nuclei of the auditory system and a low level was observed in the IC at the age P8. AT2 receptors were present at ventral cochlear nucleus and superior olivary complex, being higher at P15 and P8, respectively. We also explored the effect of prenatal administration of Ang II or PD123319 (AT2 antagonist) on binding of Ang II receptors at P0, P8, P15. Both treatments increased significantly the level of AT2 receptors at P0 and P8 in the IC. Although total binding in the whole IC from P15 animals showed no difference between treatments, the central nucleus of the IC exhibited higher binding. Our results supports a correlation between the timing of the higher expression of Ang II AT2 receptors in different nuclei, the onset of audition and the establishment of neuronal circuits of the auditory pathway.
Assuntos
Angiotensina II/efeitos dos fármacos , Vias Auditivas/efeitos dos fármacos , Vias Auditivas/metabolismo , Imidazóis/farmacologia , Piridinas/farmacologia , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Fatores Etários , Angiotensina II/metabolismo , Animais , Autorradiografia/métodos , Feminino , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , Gravidez , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismoRESUMO
Low doses of mercury (Hg) promote deleterious effects on cardiovascular system, but the mechanisms implicated remain unclear. This study analyzed whether angiotensin II AT-1 receptors are involved in the vascular dysfunction caused by chronic exposure to low HgCl2 doses. For this, rats were divided into four groups and untreated (saline by im injections and tap water by gavage) or treated for 30 days as follows: Mercury (HgCl2im, first dose of 4.6⯵gâ¯kg-1 and subsequent doses of 0.07⯵gâ¯kg-1 day-1, and tap water by gavage); Losartan (saline im and losartan, 15â¯mgâ¯kg-1 day-1, by gavage); Losartan-Mercury (HgCl2im and Losartan by gavage). Systolic blood pressure was measured by tail plethysmography, vascular reactivity in aorta by isolated organ bath, oxidative stress by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and antioxidant capacity (FRAP) and protein expression of AT-1 receptors by Western Blot. As results, co-treatment with losartan prevented the increased aortic vasoconstrictor responses to phenylephrine (Phe), the involvement of ROS and prostanoids on the response to Phe and the reduced negative endothelial modulation by nitric oxide on these responses. Moreover, this co-treatment avoided the increase in plasmatic and vascular oxidative stress and AT-1 protein expression in aorta. In conclusion, these results suggest that AT-1 receptors upregulation might play a key role in the vascular damage induced by Hg exposure by increasing oxidative stress and probably by reducing NO bioavailability.
Assuntos
Angiotensina II , Mercúrio , Estresse Oxidativo , Receptor Tipo 1 de Angiotensina , Receptores de Angiotensina , Angiotensina II/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular , Mercúrio/toxicidade , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores de Angiotensina/efeitos dos fármacos , Receptores de Angiotensina/metabolismo , Regulação para Cima , VasoconstriçãoRESUMO
Existen evidencias que apoyan la participación de las especies reactivas de oxígeno en las cascadas de señalización y transducción intracelular de la angiotensina II. La ANG II es importante en el mantenimiento de la homeostasis corporal, regulando la presión arterial y el metabolismo de fluidos y electrolitos. Se sabe que en la periferia, la ANG II es capaz de estimular a la NAD(P)H oxidasa con la subsiguiente producción de ERO. El anión superóxido es metabolizado secuencialmente por las enzimas antioxidantes como la superóxido dismutasa, la catalasa y la glutatión peroxidasa. A su vez, las especies reactivas de oxígeno son capaces de activar a las proteínas kinasas activadas por mitógenos, las cuales se encuentran asociadas al crecimiento y la diferenciación celular. Se evaluó la posible participación de las especies reactivas de oxígeno en el mecanismo de señalización intracelular mediado por el receptorAT1en el hipotálamo, el órgano subfornicaly médula suprarrenal de la rata. Nuestros resultados demostraron que la estimulación del tejido nervioso con ANG II in vitroincrementó la actividad de la enzimas antioxidante. Al evaluar el papel del receptor AT1, la NAD(P)H oxidasa, el anión superóxido y la proteína kinasa C; así como la activación de las ERK1/2 en la señalización de la ANG II en el hipotálamo, OSF y MSR, demostramos que el bloqueo del receptor AT1con losartán, la interferencia del ensamblaje de la NAD(P)H oxidasa con apocinina, el secuestro de anión superóxido empleando un mimético de la SOD, tempol,y la inhibición de la PKC con cheleritrina, bloquearon completamente el efecto que produce la ANG II sobre las enzimas antioxidantes in vitro.Igualmente, la activación de la ERK1/2 inducida por la ANG II fue reducida por APO y LOS a nivel hipotalámico. Adicionalmente, el bloqueo del receptor AT2hipotalámico con PD123319, no bloqueo sino que mas bien potenció la respuesta de las enzimas antioxidantes y la activación de las ERK1/2 inducida por la ANG II, lo que desenmascaró el efecto contra regulatorio del receptor AT2sobre la acción de la ANG II mediada por el receptor AT1. Se sabe que durante el estrés el sistema renina angiotensina circulante y cerebral se encuentra estimulado, por lo tanto el incremento de la ANG II endógena debería desencadenar vías de señalización similares a las reportadas in vitro. Efectivamente, nuestros hallazgos demostraron que tanto,el estrés agudo inducido por la inmovilización forzada,como el estrés crónico en ratas espontáneamente hipertensas incrementaron la actividad de las enzimas antioxidantes en las tres estructuras cerebrales estudiadas. Este efecto es mediado por la vía del receptor AT1, la estimulación de la NAD(P)H oxidasa y la producción de anión superóxido ya que el tratamiento in vivo con LOS, APO y TEM fue capaz de bloquear completamente el incremento de la actividad de las enzimas antioxidantes inducidas por el estrés y por ende por la ANG II endógena.A nivel de la MSR demostramos, por primera vez, que la estimulación del receptor AT2 esta asociada a la estimulación de la NAD(P)H oxidasa, ya que la APOy el PD 123319 fueron capaces de bloquear el incremento de la actividad de las enzimas antioxidantes inducida por la ANG II. Demostrando así, que el receptor AT1en la MSR contrarregula la acción de la ANG II a través del receptor AT2.En conclusión, nuestros resultados indican que a nivel del sistema nervioso las especies reactivas de oxígeno participan en la cascada de señalización intracelular de la ANG II, y ejercen un importante papel en la respuesta al estrés y la hipertensión.
Assuntos
Animais , Ratos , Angiotensina II/agonistas , Radicais Livres/farmacocinética , Tecido Nervoso/lesões , Superóxido Dismutase/farmacologia , Técnicas In Vitro/métodos , Angiotensina II/efeitos dos fármacos , Espécies Reativas de Oxigênio/efeitos adversos , Medula Suprarrenal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Losartan/uso terapêutico , Receptor Tipo 1 de Angiotensina/agonistas , Regeneração Nervosa/efeitos dos fármacos , Sistema Nervoso/fisiopatologia , Antioxidantes/farmacocinéticaRESUMO
BACKGROUND: The present study was performed to explore the effect of exogenous infusions of atrial natriuretic peptide (ANP) on the early inflammatory response during acute sodium overload in normal rats. METHODS: Sprague Dawley rats were exposed to acute sodium overload (Na 1.5 M). Nonhypotensive doses of ANP (1 and 5 microg x kg(-1) x h(-1)) were infused simultaneously with sodium or after sodium infusion in order to evaluate prevention or reversion of the inflammatory response, respectively. We determined inflammation markers in renal tissue by immunohistochemistry. RESULTS: Creatinine clearance was not reduced in any case. Sodium tubular reabsorption increased after sodium overload (334.3 +/- 18.7 vs. control 209.6 +/- 27.0 mEq x min(-1), p < 0.05) without changes in mean arterial pressure. This increase was prevented (228.9 +/- 26.4; p < 0.05) and reversed (231.5 +/- 13.9; p < 0.05) by ANP-5 microg x kg(-1) x h(-1). Sodium overload increased the expression of: RANTES (38.4.3 +/- 0.8 vs. 2.9 +/- 0.6%, p < 0.001), transforming-growth-factor-beta(1) (35.3 +/- 1.0 vs. 5.0 +/- 0.7%, p < 0.001), alpha-smooth muscle actin (15.6 +/- 0.7 vs. 3.1 +/- 0.3%, p < 0.001), NF-kappaB (9.4 +/- 1.3 to 2.2 +/- 0.5 cells/mm(2), p < 0.001), HIF-1alpha (38.2 +/- 1.7 to 8.4 +/- 0.8 cells/mm(2), p < 0.001) and angiotensin II (35.9 +/- 1.3 to 8.2 +/- 0.5%, p < 0.001). ANP-5 microg x kg(-1) x h(-1) prevented and reversed inflammation: RANTES (9.2 +/- 0.5 and 6.9 +/- 0.7, p < 0.001); transforming growth factor-beta(1) (13.2 +/- 0.7 and 10.2 +/- 0.5, p < 0.001) and alpha-smooth muscle actin (4.1 +/- 0.4 and 5.2 +/- 0.4, p < 0.001). Both prevention and reversion by ANP were associated with downregulation of NF-kappaB (3.2 +/- 0.4 and 2.8 +/- 0.5, p < 0.001) and angiotensin II (8.2 +/- 0.5 and 9.1 +/- 0.7, p < 0.001) and diminished hypoxia evaluated through HIF-1alpha expression (8.4 +/- 0.8 and 8.8 +/- 0.7, p < 0.001). CONCLUSION: Our study provides evidence supporting a protective role of ANP in both prevention and reversion of renal inflammation in rats with acute sodium overload.
Assuntos
Fator Natriurético Atrial/uso terapêutico , Nefrite Intersticial/tratamento farmacológico , Angiotensina II/efeitos dos fármacos , Animais , Fator Natriurético Atrial/farmacologia , Hipóxia/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Medula Renal/metabolismo , Túbulos Renais/metabolismo , Masculino , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/metabolismo , Ratos , Ratos Sprague-Dawley , Solução Salina Hipertônica , Sódio/metabolismoRESUMO
BACKGROUND: Angiotensin II (AII) has been shown to contribute to the pathogenesis of hypertension and insulin resistance. In addition, the administration of selective AII type 1 receptor blockers has been shown to improve insulin sensitivity. However, only a few studies have addressed the molecular mechanisms involved in this association. Furthermore, in a previous study we illustrated that obese Zucker rats (OZR) present increased serine 994 (Ser994) phosphorylation of hepatic insulin receptor, and this event seems to be implicated in the regulation of the intrinsic IRK in this model of insulin resistance. OBJECTIVE AND DESIGN: We examined the effects of chronic treatment with irbesartan (50 mg/kg a day for 6 months) on the hepatic insulin signaling system of OZR. METHODS: The extent of phosphorylation of several components of the insulin signaling system was assessed by immunoprecipitation, followed by immunoblotting with phosphospecific antibodies. In addition, liver AII levels and fat deposits were determined by immunohistochemistry and Oil red O, respectively. RESULTS: OZR displayed a marked attenuation in the in-vivo phosphorylation of several components of the insulin signaling pathways in the liver, together with significantly higher hepatic AII levels and hepatic steatosis when compared with lean Zucker rats. We found that in the livers of OZR long-term administration of irbesartan is associated with: (i) increased insulin-stimulated insulin receptor tyrosine phosphorylation; (ii) decreased insulin receptor Ser994 phosphorylation; (iii) augmented insulin receptor substrate (IRS) 1 and 2 abundance and tyrosine phosphorylation; (iv) augmented association between IRS and the p85 regulatory subunit of phosphatidylinositol 3-kinase; (v) increased insulin-induced Akt phosphorylation; and (vi) decreased hepatic steatosis. CONCLUSION: The present study provides substantial information that demonstrates that long-term selective AII blockade by irbesartan improves insulin signaling and is associated with decreased insulin receptor Ser994 phosphorylation in the liver of a representative animal model of the human metabolic syndrome.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Anti-Hipertensivos/farmacologia , Compostos de Bifenilo/farmacologia , Resistência à Insulina , Obesidade/metabolismo , Obesidade/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tetrazóis/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Análise de Variância , Angiotensina II/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/urina , Pressão Sanguínea , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/fisiopatologia , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Proteínas Substratos do Receptor de Insulina , Peptídeos e Proteínas de Sinalização Intracelular/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Irbesartana , Masculino , Proteína Quinase 3 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/efeitos dos fármacos , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Ratos , Ratos Zucker , Receptor de Insulina/efeitos dos fármacos , Receptor de Insulina/metabolismo , Proteínas Adaptadoras da Sinalização Shc , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de SrcRESUMO
AIM: To evaluate the effects of combined treatment of an ACE inhibitor and an angiotensin II receptor antagonist on parameters related to the progression of renal disease in type 2 diabetic patients. METHODS: 20 hypertensive type 2 diabetic patients with non-nephrotic proteinuria (0.5 - 3.0 g/day) and estimated creatinine clearance > or = 40 ml/min/1.73m2 were randomly assigned to be treated with perindopril 8 mg/day (Per), irbesartan 300 mg/day (Irb) or a combination of both with the same doses (Per + Irb). Each treatment phase lasting 16 weeks was preceded by a four-week washout period. Diuretics, clonidine and hydralazine were used as supplementary drugs for blood pressure control. Patients were evaluated at baseline and at the end of each treatment phase. RESULTS: 15 (3M/12F) patients completed all the phases. Use of Per, Irb and Per + Irb led to a reduction in 24-hour mean blood pressure of 6 mmHg, 4 mmHg and 4 mmHg, respectively. Changes in glomerular filtration rate were not significant at any phase. Renal plasma flow was significantly more elevated with Irb than Per. Treatment with both Irb and Per + Irb induced similar plasma renin elevation, but treatment with Per did not, suggesting escape. Plasma aldosterone was reduced only by treatment with Per + Irb (-36%, p < 0.02). Reduction in proteinuria during Per + Irb (-33%) was not significantly different from Per (-34%) or Irb (-22%). Urinary transforming growth factor beta1 (TGF-beta1) excretion was significantly reduced with both Irb (-24%, p < 0.05) and Per + Irb (-36%, p < 0.05) but not with Per (-11%, p = 0.60). CONCLUSION: Only combined therapy with irbesartan plus perindopril concurrently reduces plasma aldosterone, proteinuria and urinary TGF-beta1.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Hipertensão/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Idoso , Aldosterona/sangue , Angiotensina II/sangue , Angiotensina II/efeitos dos fármacos , Biomarcadores/sangue , Compostos de Bifenilo/uso terapêutico , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/complicações , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Irbesartana , Masculino , Pessoa de Meia-Idade , Perindopril/uso terapêutico , Renina/sangue , Renina/efeitos dos fármacos , Tetrazóis/uso terapêutico , Resultado do TratamentoRESUMO
The effects of 1 nM ouabain (OUA) on the contractile actions of phenylephrine (PHE, 0.001-100 microg) and functional activity of the sodium pump (NKA) in isolated-perfused tail vascular beds from WKY and SHR were investigated. In preparations from SHR, perfusion with OUA in the presence of endothelium (E+) increased the sensitivity (pED50) of PHE (before: 2.14 +/- 0.06 versus after: 2.47 +/- 0.07; P < 0.05) without altering the maximal response (Emax). After endothelial damage, OUA reduced the Emax of PHE in SHR (before: 350 +/- 29 versus after: 293 +/- 25 mm Hg; P < 0.05). In SHR/E+, pretreatment with losartan (10 microM) or enalaprilat (1 microM) prevented the increased sensitivity to PHE induced by OUA. OUA increased NKA activity in SHR/E+ (before: 45 +/- 6 versus after: 58 +/- 5%, P < 0.05). Losartan (10 mg/Kg, i.v.) also abolished the increment in systolic and diastolic blood pressure induced by OUA (0.18 microg/Kg, i.v.) in anesthetized SHR. OUA did not alter the actions of PHE in either anesthetized WKY rats or vascular preparations. Results suggest that 1 nM OUA increased the vascular reactivity to PHE only in SHR/E+. This effect is mediated by OUA-induced activation of endothelial angiotensin converting enzyme that promotes the local formation of angiotensin II, which sensitizes the vascular smooth muscle to the actions of PHE.
Assuntos
Angiotensina II/metabolismo , Endotélio Vascular/metabolismo , Ouabaína/farmacocinética , Cauda/citologia , Angiotensina II/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Sinergismo Farmacológico , Quimioterapia Combinada , Enalaprilato/farmacologia , Glucose/administração & dosagem , Glucose/química , Hexametônio/farmacologia , Injeções Intravenosas , Losartan/antagonistas & inibidores , Losartan/farmacologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Ouabaína/administração & dosagem , Perfusão , Fenilefrina/farmacologia , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , ATPase Trocadora de Sódio-Potássio/fisiologia , Cauda/irrigação sanguínea , Cauda/metabolismo , Fatores de Tempo , Trometamina/administração & dosagem , Trometamina/química , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologiaAssuntos
Humanos , Técnicas In Vitro , Camundongos , Arteriosclerose/tratamento farmacológico , Ácido Ascórbico/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Camundongos Transgênicos , Arteriosclerose/prevenção & controle , Ácido Ascórbico/farmacologia , Deficiência de Ácido Ascórbico/complicações , Ensaios Clínicos como Assunto , Resultado do Tratamento , Insuficiência Cardíaca/fisiopatologia , Apoptose/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Angiotensina II/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Substâncias Reativas com Ácido Tiobarbitúrico , Antioxidantes/uso terapêuticoRESUMO
En los receptores de transplante renal se han detectado diversos trastornos de la acidificación urinaria atribuyendo éste hecho a la nefrotoxicidad producida por inmunosupresores. Se estudió el efecto de la ciclosporina A (CyA) sobre la excreción de amonio (NH4+), su relación con la pérdida de un precursor, la gamma glutamiltranspeptidasa urinaria (GGTu), tratando de aportar al conocimiento de los cuadros de acidosis. Para ello se estudiaron 12 pacientes transplantados renales con esquemas que incluían ciclosporina A. Las muestras obtenidas de éstos pacientes fueron divididas en dos grupos, de acuerdo con los niveles de ciclosporina en sangre. Grupo A: con concentraciones de CyA entre 260 y 600 ng/ml, aumento de la creatinina sérica y diagnóstico de nefrotoxicidad dado por biopsia aspirativa con aguja fina. Grupo B: con concentraciones de CyA entre 120 y 200 ng/ml y creatinina estable, con variaciones menores del 15 por ciento. Grupo C: 87 individuos sanos sin medicación. Se usaron muestras de sangre para medir CyA, por polarización inmunofluorescente con anticuerpos monoclonales; la creatinina sérica fue determinada por el método de Jaffé modificado y el amonio en orina con Ammonia Reagent Kit. Los resultados muestran que las concentraciones de NH4+ para los grupos A y B con respecto a C no dieron diferencias significativas (NS); el grupo A presentó valores elevados de GGTu(52,4 ñ 16 U/l) y de creatinina sérica (2,3 ñ 0,8 mg/dl) siendo ambas diferencias significativas (p < 0,05) con respecto a C, mientras que el grupo B mostró aumento en los niveles de la enzima (27,8 ñ 3,1 U/l) sin modificación de la creatinina sérica (1,2 ñ 0,2 mg/dl). De éstos resultados se concluye que: la CyA, aún a dosis altas (grupo A) no afecta la síntesis de amoníaco; la enzima de membrana GGT, mediante el mecanismo de glutaminasa GPI-P independiente, no sería el factor más importante en la síntesis de NH3 y que el efecto vasocontrictor, por falla en la conversión de angiotensina II, contribuiría a regular el estado ácido-base del paciente tratado co CyA (AU)