RESUMO
OBJECTIVE: To analyze the clinical characteristics, diagnosis, treatment and outcome of patients with cardiac amyloidosis (CA). METHODS: Clinical data from 18 patients diagnosed as CA by endomyocardial biopsy (EMB) from 1995 to 2005 were retrospectively analyzed. RESULTS: Among the 18 patients with CA, all patients had reduced diastolic dysfunction; 12 had mitral valve early diastolic blood flow peak velocity/late diastolic blood flow peak velocity (E/A) > 2.0 and ventricular diastolic early filling deceleration time (DT) < 150 ms; 12 had left ventricular ejection fraction (LVEF) < 50%; and 13 had New York Heart Association (NYHA) classification III or IV. The 1-year, 3-year and 5-year survival rates of 18 patients with CA were 67%, 44% and 17%, respectively. Kaplan-Meier analysis showed, NYHA functional class > II, E/A > 2.0 and DT < 150 ms were associated with increased mortality (log-rank statistic P = 0.026 and 0.001, respectively). CA patients with chemotherapy before heart failure were associated with decreased mortality and extend survival. CONCLUSIONS: The mortality rate goes up and survival rate gradually descends as prolonged onset time. NYHA functional class >IIand E/A > 2.0 (DT< 150 ms) are associated with mortality.
Assuntos
Amiloidose/patologia , Insuficiência Cardíaca/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Amiloidose/mortalidade , Biópsia , Cateterismo Cardíaco , Cardiomiopatias , Diástole/fisiologia , Ecocardiografia Doppler , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Humanos , Estimativa de Kaplan-Meier , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular EsquerdaRESUMO
OBJECTIVE: The aim of our study was to investigate the prevalence of target organ damage (TOD) in elderly hypertensive inpatients. METHODS: Data of the present retrospective survey were collected and analyzed from the computerized medical records of 17 682 aged 60 years or older inpatients with the diagnosis of essential hypertension (EH) from January 1993 to December 2008 in our hospital. The evidences of hypertensive TOD and associated risk factors with TOD including age, gender, presence of diabetes (DM), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP), serum lipids were analyzed. RESULTS: The overall prevalence of stroke, coronary artery disease (CAD), chronic kidney disease (CKD) and aortic dissection (AD) was 32.19%, 27.33%, 10.12% and 0.77%, respectively. Incidence of TOD was 68.03% in male and 31.70% in female patients. CKD stage 3-5 was more prevalent in males than in females (12.75% vs. 5.40%, P < 0.01), while the prevalence of CAD (31.31% vs. 27.96%, P = 0.06), Stroke (28.23% vs. 25.81%, P = 0.08) and AD (0.89% vs.0.74%, P = 0.72) was similar between men and women. One TOD was presented in 23.20% patients and two or more TODs were found in 47.19% patients. Higher age and BMI, longer history and lower control rate of hypertension, severe degree of hypertension and higher level of SBP, pulse pressure, TC, LDL-C, estimated GFR (eGFR) and Hcy were risk factors for TOD. BMI, fasting plasma glucose, incidence of DM, prevalence of stage 1 and 2 hypertension, control rate of hypertension, eGFR and TG levels were all significantly higher while the prevalence of hypertension stage 3 and level of TC and LDL-C were significantly lower in female TOD patients than in male TOD patients (all P < 0.05). In patients without TOD, TG was significantly higher while SBP, fasting plasma glucose and LDL-C were significantly lower and history of hypertension was significantly shorter in female patients than in male patients (all P < 0.05). The prevalence of CAD, stroke and CKD increased with age (P < 0.001). CONCLUSION: The prevalence of TOD is high in elderly hypertensive inpatients and higher age and BMI, longer history and lower control rate of hypertension, severe degree of hypertension and higher level of SBP, pulse pressure, TC, LDL-C, eGFR and Hcy are risk factors for TOD.
Assuntos
Doenças da Aorta/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Hipertensão/complicações , Nefropatias/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doenças da Aorta/complicações , Doença da Artéria Coronariana/complicações , Feminino , Humanos , Hipertensão/epidemiologia , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
AIM: To investigate the effects of iptakalim on endothelial dysfunction induced by insulin resistance (IR) and to determine whether iptakalim improved IR associated with hypertension in fructose-fed rats (FFRs) and spontaneously hypertensive rats (SHRs). METHODS: Human umbilical vein endothelial cells (HUVECs) were used for in vitro study. The levels of endothelial vasoactive mediators and eNOS protein expression were determined using radioimmunoassays, ELISAs, colorimetric assays or Western blotting. Sprague-Dawley rats were fed with a high-fructose diet. In both FFRs and SHRs, tail-cuff method was used to measure systolic blood pressure (SBP), and hyperinsulinemic- euglycemic clamp was used to evaluate IR states. RESULTS: (1) Cultured HUVECs incubated with the PI3-kinase inhibitor wortmannin (50 nmol/L) and insulin (100 nmol/L) induced endothelial dysfunction characterized by significantly reduced release of NO and expression of eNOS protein, and significantly increased production of ET-1. Pretreatment with iptakalim (0.1-10 µmol/L) could prevent the endothelial dysfunction. (2) In FFRs, the levels of SBP, fasting plasma glucose and insulin were significantly elevated, whereas the glucose infusion rate (GIR) and insulin sensitive index (ISI) were significantly decreased, and the endothelium-dependent vascular relaxation response to ACh was impaired. These changes could be prevented by oral administration of iptakalim (1, 3, or 9 mg·kg(-1)·d(-1), for 4 weeks). The imbalance between serum NO and ET-1 was also ameliorated by iptakalim. (3) In 2-4 month-old SHRs (IR was established at the age of 4 months), oral administration of iptakalim (1, 3, or 9 mg·kg(-1)·d(-1), for 8 weeks) significantly ameliorated hypertension and increased the GIR to the normal level. CONCLUSION: These results demonstrate that iptakalim could protect against IR-induced endothelial dysfunction, and ameliorate IR associated with hypertension, possibly via restoring the balance between NO and ET-1 signaling.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Hipertensão/prevenção & controle , Resistência à Insulina , Canais KATP/agonistas , Propilaminas/farmacologia , Animais , Células Cultivadas , Endotélio Vascular/fisiologia , Humanos , Hipertensão/fisiopatologia , Masculino , Radioimunoensaio , Ratos , Ratos Endogâmicos SHRRESUMO
BACKGROUND AND OBJECTIVES: It has been demonstrated that hyperuricemia induces reno-cardiovascular damage resulting in hypertension and renal injury because of vascular endothelial dysfunction. The pathogenesis of hyperuricemia, endothelial dysfunction, hypertension, and renal injury is progressive, and develops into a vicious cycle. It is reasonable to suggest that an antihypertensive drug with endothelial protection may block this vicious cycle. Iptakalim, a novel antihypertensive drug undergoing phase-three clinical trials, is a new ATP-sensitive potassium channel opener and can ameliorate endothelial dysfunction. We hypothesized that iptakalim could prevent hypertension and retard the pathogenesis of endothelial dysfunction and renal injury in hyperuricemic rats. METHODS AND RESULTS: In rats with hyperuricemia induced by 2% oxonic acid and 0.1 mmol/l uric acid, iptakalim prevented increases in systolic blood pressure, reduced the impairment of endothelial vasodilator function, and attenuated renal dysfunction and pathological changes in glomerular and renal interstitial tissue at 0.5, 1.5, and 4.5 mg/kg orally daily for 4 weeks. Serum levels of nitric oxide and prostacyclin, and gene expression of endothelial nitric oxide synthase in the aortic and intrarenal tissue, were increased, whereas the serum levels of endothelin-1 and gene expression of endothelin-1 in aortic and intrarenal tissue were decreased. However, serum levels of angiotensin II and renin remained unchanged in the hyperuricemic rats treated with iptakalim. In cultured rat aortic endothelial cells, amelioration of endothelial dysfunction by iptakalim was suggested by inhibition of the overexpression of intercellular adhesive molecule-1, vascular cell adhesive molecule-1, and monocyte chemoattractant protein-1 mRNA induced by uric acid, and reversal of the inhibitory effects of uric acid on nitric oxide release in a concentration-dependent manner, which could be abolished by pretreatment with glibenclamide, an ATP-sensitive potassium channel blocker. Iptakalim ameliorated hyperuricemia in this rat model by decreasing renal damage through its antihypertensive and endothelial protective properties, and it had no direct effects on anabolism, catabolism and excretion of uric acid. CONCLUSION: These findings suggest that the activation of ATP-sensitive potassium channels by iptakalim can protect endothelial function against hypertension and renal injury induced by hyperuricemia. Iptakalim is suitable for use in hypertensive individuals with hyperuricemia.
Assuntos
Endotélio Vascular/metabolismo , Hipertensão/prevenção & controle , Hiperuricemia/complicações , Canais KATP/metabolismo , Nefropatias/prevenção & controle , 6-Cetoprostaglandina F1 alfa/metabolismo , Angiotensina II/metabolismo , Angiotensinas , Animais , Células Cultivadas , Modelos Animais de Doenças , Endotelina-1/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Hiperuricemia/induzido quimicamente , Hiperuricemia/metabolismo , Canais KATP/agonistas , Canais KATP/efeitos dos fármacos , Rim/irrigação sanguínea , Rim/patologia , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Masculino , Óxido Nítrico/metabolismo , Ácido Oxônico/metabolismo , Propilaminas/farmacologia , Propilaminas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Urato Oxidase/metabolismo , Ácido Úrico/metabolismo , Xantina Oxidase/metabolismoRESUMO
OBJECTIVE: To investigate the experimental therapeutic effects of iptakalim hydrochloride (Ipt) on renoprotection in spontaneously hypertensive rats. METHODS: 30 SHR were treated ig with Ipt 1, 3, 9 mg.kg(-1).d(-1), benazepril 3 mg.kg(-1).d(-1) once a day for 12 weeks. Age-matched WKY rats were used as normal control. The blood pressure, heart rates, proteinuria were assessed, and renal tissues were examined by light microscopy. The levels of blood and renal tissue ET-1 and TGF-beta1 were detected respectively by radioimmunoanalysis and enzyme linked immune absorption assay (ELISA). RESULTS: During 12 weeks experimental period, the systolic blood pressure (SBP) and heart rates (HR) of the untreated SHR were increased progressively. Ipt (3, 9 mg.kg(-1).d(-1)) could decrease effectively and inhibit the increasing tendency of HR. In addition, Ipt (1, 3, 9 mg.kg(-1).d(-1)) reduced urinary proteinuria, alleviated obviously the small vascular remodeling of renal and decreased the levels blood and renal ET-1 and TGF-beta1. Ipt (3, 9 mg.kg(-1).d(-1)) alleviated obviously the small vascular remodeling of renal compared with Ipt (1 mg.kg(-1).d(-1)). CONCLUSIONS: Ipt (1, 3, 9 mg.kg(-1).d(-1)) decreased SBP and protected the kidney of SHR. The renoprotection of Ipt may be involved in inhibiting of blood and renal tissue ET-1 and TGF-beta1.
Assuntos
Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Rim/efeitos dos fármacos , Propilaminas/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotelina-1/metabolismo , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fator de Crescimento Transformador beta/metabolismoRESUMO
OBJECTIVE: To explore the role of hypoxia in skeletal myoblasts proliferation and related mechanism. METHODS: The numbers and proliferous indexes of skeletal myoblasts were detected by flow cytometer under 20%, 3%, and 10% oxygen concentration. Hypoxia inducing factor 1alpha (HIF-1alpha) mRNA expression was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). HIF-1alpha proteinum in endochylema and intranucelus were respectively detected by Western blot. RESULTS: The numbers and proliferous indexes were higher (P < 0.05) in hypoxia group than those of control group. The expression HIF-1alpha mRNA had no difference in hypoxia and in normal groups. The level of HIF-1alpha proteinum in endochylema under normoxia was more than that in intranucelus and it was opposite under hypoxia. CONCLUSION: Hypoxia can promote the proliferation of skeletal myoblasts. The possible mechanism of hypoxia promoting the proliferation of skeletal myoblasts might be that low oxygen concentration regulates HIF-la nuclear translocation.
Assuntos
Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/metabolismo , Oxigênio/metabolismo , Animais , Hipóxia Celular , Células Cultivadas , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
The effects of iptakalim, a new ATP-sensitive potassium channel opener, were studied in spontaneously hypertensive rats (SHR). Treatment of 12-week-old male SHR (six animals in each group) with iptakalim by gastric lavage at doses of 1, 3, or 9 mg/kg/day for 12 weeks resulted in a lowering of blood pressure. Iptakalim provided significant renoprotection to SHR rats as measured by decreased proteinuria and improved renal function. Histological evidence demonstrated that iptakalim could reverse renal vascular remodeling (of afferent arterioles, arcuate arteries, or interlobular arteries), and improve pathological changes of glomerular, renal interstitial, and glomerular filtration membranes. These effects were accompanied by the decreased circulation and intrarenal concentrations of endothelin 1 and transforming growth factor beta1 (TGF-beta1), and down-regulated overexpression of genes for ET-1, endothelin-converting enzyme 1, TGF-beta1, and the subunits of ATP-sensitive potassium channels (K(ATP)), Kir1.1 and Kir6.1, in the kidney during hypertension. Abnormal expression of matrix components [collagen IV, fibronectin, matrix metalloproteinase 9 (MMP-9) and MMP tissue inhibitor 1 (TIMP-1)] was also significantly reversed by iptakalim. Our results demonstrate that chronic treatment with iptakalim not only reduces blood pressure but also preserves renal structure and function in SHR. In addition to reducing blood pressure, the renoprotective of iptakalim may be involved in inhibiting the circulation and intrarenal concentrations of endothelin 1 and TGF-beta1, regulating the expression of K(ATP) genes and correcting MMP-9/TIMP-1 imbalance in renal tissue, which may result in reducing the accumulation of extracellular matrix molecules.
Assuntos
Transportadores de Cassetes de Ligação de ATP/agonistas , Hipertensão/patologia , Nefropatias/etiologia , Nefropatias/prevenção & controle , Rim/patologia , Canais de Potássio Corretores do Fluxo de Internalização/agonistas , Propilaminas/uso terapêutico , Angiotensina II/sangue , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Hipertensivos/uso terapêutico , Benzazepinas/uso terapêutico , Endotelina-1/sangue , Matriz Extracelular/patologia , Hemodinâmica , Hipertensão/genética , Imuno-Histoquímica , Canais KATP , Nefropatias/patologia , Testes de Função Renal , Ratos , Ratos Endogâmicos SHR , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta1RESUMO
AIM: To compare the differences of pharmacological characteristics of the endothelial target for acetylcholine (ETA) between rat aorta and tail artery. METHODS: Differences in the endothelium-dependent relaxation induced by acetylcholine (ACh: 10(-8) - 10(-4) mol/L) were studied using isolated rat tail artery helical strips and aortic rings, so that the pharmacological characteristics of ETA in small artery can be observed. RESULTS: ACh-induced endothelium-dependent relaxation was observed both in rat tail artery strips and in aortic rings precontracted with potassium chloride (60 mmol/L) in a concentration-dependent manner. In tail artery this effect was partially blocked by L-N(omega)-Nitro-arginine methyl ester (L-NAME: 10(-4) mol/L) or methylene blue (MB: 10(-5) mol/L), together with indomethacin (Indo: 10(-4) mol/L), but in aorta it was completely blocked by L-NAME or MB. CONCLUSION: It is different of the pharmacological characteristics of ETA between big artery and small artery. A non-NO and non-PGI2 relaxing factor, together with nitric oxide (NO) and prostacyclin (PGI2), mediates endothelium-dependent vasorelaxation induced by ACh in small artery, but NO may be the principal endothelial vasodilator substance in big artery.