RESUMO
Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.
Assuntos
Animais , Masculino , Coelhos , Acetilcolina/administração & dosagem , Acidose/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Hipotensão/induzido quimicamente , Doença Aguda , Desequilíbrio Ácido-Base/metabolismo , Acidose/induzido quimicamente , Acidose/metabolismo , Determinação da Pressão Arterial , Bicarbonatos/sangue , Pressão Sanguínea/fisiologia , Doença Crônica , Dióxido de Carbono/análise , Endotélio Vascular/metabolismo , Hemodinâmica/fisiologia , Hiperventilação/metabolismo , Luminescência , Nitratos/sangue , Óxido Nítrico/metabolismo , Nitritos/sangueRESUMO
ObjectiveThere is a growing body of data supporting the association between diabetes and microcirculatory disfunction. We aimed to study e-selectin levels, and their associations with serum markers of inflammation and arterial stiffness in prediabetes and newly diagnosed diabetes patients in this study.Subjects and methodsSixty patients (25 females) with a newly established elevated fasting serum glucose [20 impaired fasting glucose (IFG), 20 impaired glucose tolerance (IGT), 20 newly diagnosed diabetes (T2DM)] and 17 healthy controls (13 females) were included in the study. Serum e-selectin and hs-CRP levels, and arterial stiffness parameters of the patients were studied.ResultsFasting serum glucose was the most important predictor of serum e-selectin levels. Pulse wave velocity and central aortic pressures were significantly higher in IFG, IGT and T2DM groups, compared to controls (p = 0.001, < 0.001, 0.013 and 0.015, 0.002, 0.009, respectively). The mean arterial pressure did not show any significant association with serum e-selectin and hs-CRP levels (β coefficient: 0.092, p = 0.358; and β coefficient: 0.189, p = 0.362, respectively).ConclusionPrediabetes patients have increasing e-selectin levels through the diagnosis of T2DM. E-selectin is associated with serum glucose levels. Prediabetic and newly diagnosed diabetics have higher arterial stiffness measurements. Serum e-selectin may be a good marker of endothelial inflammation and dysfunction increasing in parallel with serum glucose levels, predicting future cardiovascular events.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína C-Reativa/análise , /metabolismo , Selectina E/sangue , Endotélio Vascular/metabolismo , Estado Pré-Diabético/metabolismo , Rigidez Vascular/fisiologia , Biomarcadores/sangue , Glicemia/análise , Estudos de Casos e Controles , /fisiopatologia , Endotélio Vascular/fisiopatologia , Jejum/sangue , Teste de Tolerância a Glucose , Microcirculação , Análise de Onda de Pulso , Estado Pré-Diabético/fisiopatologia , Fatores de RiscoRESUMO
Introdução: A disfunção endotelial é importante na patogênese da doença cardiovascular (DCV) relacionada à doença renal crônica (DRC). Stromal cell-derived factor-1 (SDF-1) é uma quimiocina que mobiliza células endoteliais progenitoras (EPC) e em conjunto com a interleucina-8 (IL-8) podem ser usadas como marcadores de reparo e lesão tecidual. Objetivo: Neste trabalho, foi investigado o efeito do meio urêmico na expressão de SDF-1 e IL-8 in vivo e in vitro. Métodos: A inflamação sistêmica foi avaliada por meio da proteína C-reativa (PCR) e interleucina-6 (IL-6). IL-8 e SDF-1 foram avaliados por ELISA como marcadores de disfunção endotelial e reparo tecidual, respectivamente. Os estudos in vitro foram realizados em células endoteliais umbilicais humanas (HUVEC) expostas ao meio urêmico ou saudável. Resultados: Foram incluídos nesse estudo 26 pacientes em hemodiálise (HD) (17 ± 3 meses em diálise, 52 ± 2 anos, 38% homens e 11% diabéticos). As concentrações séricas de PCR, IL-6, SDF-1 e IL-8 foram 4,9 ± 4,8 mg/ml, 6,7 ± 8,1 pg/ml, 2625,9 ± 1288,6 pg/ml e 128,2 ± 206,2 pg/ml, respectivamente. Houve correlação positiva entre PCR e IL-6 (ρ = 0,57; p < 0,005) e entre SDF-1 e IL-8 (ρ = 0,45; p < 0,05). Os resultados in vitro demonstraram que a expressão de SDF-1 pelas HUVEC após 6 horas de tratamento com meio urêmico é menor comparada ao tratamento com meio saudável (p < 0,05). Após 12 horas de tratamento, ocorreu aumento de IL-8 quando as HUVECs foram expostas ao meio urêmico (p < 0,005). Conclusão: Sugerimos que SDF-1 e IL-8 nos pacientes em HD podem ser usados para mensurar a extensão do dano e consequente ativação vascular na uremia. .
Introduction: Endothelial dysfunction is important in the pathogenesis of cardiovascular disease (CVD) related to chronic kidney disease (CKD). Stromal cell-derived factor-1 (SDF-1) is a chemokine which mobilizes endothelial progenitor cells (EPC) and together with interleukin-8 (IL-8) may be used as markers of tissue injury and repair. Objective: This study investigated in vivo and in vitro the effect of uremic media on SDF-1 and IL-8 expression. Methods: Systemic inflammation was assessed by C-reactive protein (CRP) and interleukin-6 (IL-6). IL-8 and SDF-1 were measured as markers of endothelial dysfunction and tissue repair, respectively, by ELISA. In vitro studies were performed on human umbilical vein endothelial cells (HUVEC) exposed to healthy or uremic media. Results: The study included 26 hemodialysis (HD) patients (17 ± 3 months on dialysis, 52 ± 2 years, 38% men and 11% diabetic). Serum concentrations of CRP, IL-6, SDF-1 and IL-8 were 4.9 ± 4.8 mg/ml, 6.7 ± 8.1 pg/ml, 2625.9 ± 1288.6 pg/ml and 128.2 ± 206.2 pg/ml, respectively. There was a positive correlation between CRP and IL-6 (ρ = 0.57, p < 0.005) and between SDF-1 and IL-8 (ρ = 0.45, p < 0.05). In vitro results showed that after 6 hours treatment, SDF-1 expression by HUVEC treated with uremic media is lower compared to cells treated with healthy media (p < 0.05). After 12 hours of treatment there was an increase in IL-8 when HUVECs were exposed to uremic media (p < 0.005). Conclusion: We suggest that SDF-1 and IL-8 in HD patients can be used to measure the extent of damage and subsequent vascular activation in uremia. .
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , /biossíntese , /biossíntese , Falência Renal Crônica/sangue , Uremia/sangue , Fenômenos Fisiológicos Sanguíneos , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Falência Renal Crônica/terapia , Diálise Renal , Uremia/terapiaRESUMO
Atherosclerotic coronary heart disease is the leading cause of morbidity and mortality in industrialized countries, and endothelial dysfunction is considered a precursor phenomenon. The nitric oxide produced by the endothelium under the action of endothelial nitric oxide synthase has important antiatherogenic functions. Its reduced bioavailabilty is the beginning of the atherosclerotic process. The addition of two methyl radicals to arginine, through the action of methyltransferase nuclear proteins, produces asymmetric dimethylarginine, which competes with L-arginine and promotes a reduction in nitric oxide formation in the vascular wall. The asymmetric dimethylarginine, which is itself considered a mediator of the vascular effects of the several risk factors for atherosclerosis, can be eliminated by renal excretion or by the enzymatic action of the dimethylarginine dimethylaminohydrolases. Several basic science and clinical research studies suggest that the increase in asymmetric dimethylarginine occurs in the context of chronic renal insufficiency, dyslipidemia, high blood pressure, diabetes mellitus, and hyperhomocysteinemy, as well as with other conditions. Therapeutic measures to combat atherosclerosis may reverse these asymmetric dimethylarginine effects or at least reduce the concentration of this chemical in the blood. Such an effect can be achieved with competitor molecules or by increasing the expression or activity of its degradation enzyme. Studies are in development to establish the true role of asymmetric dimethylarginine as a marker and mediator of atherosclerosis, with possible therapeutic applications. The main aspects of the formation and degradation of asymmetric dimethylarginine and its implication in the atherogenic process will be addressed in this article.