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1.
J Endocrinol ; 252(3): 179-193, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-34874016

RESUMO

Compelling evidence has described that the incidence of hypertension and left ventricular hypertrophy (LVH) in postmenopausal women is significantly increased worldwide. Our team's previous research identified that androgen was an underlying factor contributing to increased blood pressure and LVH in postmenopausal women. However, little is known about how androgens affect LVH in postmenopausal hypertensive women. The purpose of this study was to evaluate the role of mammalian rapamycin receptor (mTOR) signaling pathway in myocardial hypertrophy in androgen-induced postmenopausal hypertension and whether mTOR inhibitors can protect the myocardium from androgen-induced interference to prevent and treat cardiac hypertrophy. For that, ovariectomized (OVX) spontaneously hypertensive rats (SHR) aged 12 weeks were used to study the effects of testosterone (T 2.85 mg/kg/weekly i.m.) on blood pressure and myocardial tissue. On the basis of antihypertensive therapy (chlorthalidone 8 mg/kg/day ig), the improvement of blood pressure and myocardial hypertrophy in rats treated with different dose gradients of rapamycin (0.8 mg/kg/day vs 1.5 mg/kg/day vs 2 mg/kg/day i.p.) in OVX + estrogen (E 9.6 mg/kg/day, ig) + testosterone group was further evaluated. After testosterone intervention, the OVX female rats exhibited significant increments in the heart weight/tibial length (TL), area of cardiomyocytes and the mRNA expressions of ANP, ß-myosin heavy chain and matrix metalloproteinase 9 accompanied by a significant reduction in the uterine weight/TL and tissue inhibitor of metalloproteinase 1. mTOR, ribosomal protein S6 kinase (S6K1), 4E-binding protein 1 (4EBP1) and eukaryotic translation initiation factor 4E in myocardial tissue of OVX + estrogen + testosterone group were expressed at higher levels than those of the other four groups. On the other hand, rapamycin abolished the effects of testosterone-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Collectively, these data suggest that the mTOR/S6K1/4EBP1 pathway is an important therapeutic target for the prevention of LVH in postmenopausal hypertensive female rats with high testosterone levels. Our findings also support the standpoint that the mTOR inhibitor, rapamycin, can eliminate testosterone-induced cardiomyocyte hypertrophy.


Assuntos
Hipertrofia Ventricular Esquerda/prevenção & controle , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Inibidores de MTOR/uso terapêutico , Miocárdio/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Hipertrofia Ventricular Esquerda/etiologia , Ovariectomia , Ratos Endogâmicos SHR , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Testosterona
2.
Menopause ; 28(11): 1264-1270, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34429391

RESUMO

OBJECTIVE: The present study investigated the effects of free androgen index (FAI) on ambulatory blood pressure (ABP) and target organ function in postmenopausal hypertensive women. METHODS: A total of 285 postmenopausal hypertensive women (mean age 54.06 ±â€Š3.61) were admitted to the Department of Hypertension of Lanzhou University Second Hospital between December 2018 and December 2020. According to the serum FAI level, the participants were divided into a low-FAI (<0.15) group, a medium-FAI (0.15-0.2) group, and a high-FAI (>0.2) group. The relationship of FAI with 24-hour ABP, left ventricular mass index (LVMI), and cardio-ankle vascular index (CAVI) was analyzed. RESULTS: The LVMI, CAVI, 24-hour mean systolic blood pressure (SBP), 24-hour SBP coefficient of variation and 24-hour SBP standard deviation, 24-hour SBP average real variation (ARV), and 24-hour diastolic blood pressure (DBP) ARV in high-FAI group were significantly higher than those in low- and medium-FAI groups (P < 0.05). After adjusting for confounding factors, partial correlation analysis showed that FAI was positively correlated with LVMI (r = 0.728, P < 0.001), CAVI (left: r = 0.718, P < 0.001; right: r = 0.742, P < 0.001), 24-hour SBP ARV (r = 0.817, P < 0.001), and 24-hour DBP ARV (r = 0.747, P < 0.001). After adjusting for confounding factors, it was found that LVMI increased by 17.64 g/m2 for every 1 unit increase in FAI. CAVI also increased by 8.983 for every additional unit of FAI. In addition, the results also showed that LVMI and CAVI decreased respectively by 0.198 g/m2 and 0.009 for every 1 unit increase in sex hormone-binding globulin. Multivariable linear regression showed that FAI was an independent risk factor for 24-hour SBP ARV (OR: 20.416, 95% CI 8.143-32.688, P = 0.001) and 24-hour DBP ARV (OR: 16.539, 95% CI 0.472-32.607, P = 0.044). The results also showed that sex hormone-binding globulin was an independent factor of 24-hour SBP ARV (OR: -0.022, 95% CI -0.044 to 0.000, P = 0.048) and 24-hour DBP-ARV (OR: -0.018, 95% CI -0.029 to -0.008, P = 0.001). CONCLUSION: Higher serum FAI levels in postmenopausal hypertensive women indicate abnormal BP regulation and more serious target organ damage. FAI is closely related to 24-hour SBP ARV and 24-hour DBP ARV in postmenopausal hypertensive women.


Assuntos
Androgênios , Hipertensão , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Estudos Transversais , Feminino , Humanos , Hipertrofia Ventricular Esquerda , Pessoa de Meia-Idade , Pós-Menopausa
3.
J Int Med Res ; 48(8): 300060520943453, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32790534

RESUMO

OBJECTIVE: To compare the potential beneficial effects of the angiotensin converting enzyme inhibitor (ACEI) benazepril and the angiotensin II receptor 1 blocker (ARB) irbesartan on vaginal vascular remodeling and fibrosis in female spontaneously hypertensive rats (SHRs). METHODS: Twelve-week-old female SHRs were treated with irbesartan or benazepril for 12 weeks. Vaginal renin angiotensin system (RAS) components were detected by polymerase chain reaction and western blot and vaginal α-smooth muscle actin (α-SMA), endothelial nitric oxide synthase (eNOS), and collagen III (Col III) were analyzed by western blot. Vaginal tissue sections were examined by hematoxylin and eosin staining, Masson trichrome staining, and immunohistochemical analysis of α-SMA and Col III. RESULTS: Irbesartan and benazepril had different impacts on vaginal RAS components. Both agents decreased vaginal α-SMA and Col III and increased eNOS expression in SHR. The wall/lumen thickness ratio of vaginal arterioles was similarly decreased following irbesartan and benazepril treatment. Both drugs also decreased collagen deposition in SHRs. There was no difference in vaginal vascular remodeling or fibrosis between the two groups. CONCLUSIONS: Irbesartan and benazepril have different effects on vaginal RAS expression but similar positive effects against vaginal vascular remodeling and fibrosis.


Assuntos
Antagonistas de Receptores de Angiotensina , Hipertensão , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Benzazepinas , Pressão Sanguínea , Feminino , Fibrose , Irbesartana , Ratos , Ratos Endogâmicos SHR , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Remodelação Vascular
4.
BMC Cardiovasc Disord ; 20(1): 351, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727406

RESUMO

BACKGROUND: To investigate the clinical value of heart failure echocardiography index (HFEI) in evaluating the cardiac function and predicting the prognosis of patients with different types of heart failure (HF). METHODS: Four hundred eighty-nine consecutively admitted HF patients were divided into three groups: HF with reduced ejection (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). The baseline characteristics and ultrasound indexes were compared between the three groups. The correlation between HFEI and one-year risk of adverse events was compared by multivariate logistic regression. The clinical value of HFEI and plasma level of NT-proBNP in assessing the prognosis of patients with chronic heart failure (CHF) was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: HFEI in HFrEF was significantly higher than that in HFmrEF and HFpEF. Multivariate regression analysis indicated that HFEI and plasma level of NT-proBNP were independent risk factors for predicting the short-time prognosis of HF patients. The ROC curve indicated that the HFEI cutoff level of 3.5 and the plasma NT-proBNP level of 3000 pg/ml predicted a poor prognosis of CHF patients with a sensitivity of 64% and a specificity of 75% vs. 68 and 65%. CONCLUSION: HFEI can comprehensively evaluate the overall cardiac function of patients with various types of HF, and may prove to be an important index of assessing the prognosis of HF patients.


Assuntos
Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Volume Sistólico , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
5.
Cardiovasc Ther ; 2020: 7056184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190121

RESUMO

To determine the effects of ACEIs on arterial stiffness, a meta-analysis of randomized controlled trials was conducted. Relevant articles that investigated the effects of ACEIs on arterial stiffness from PubMed, Embase, and the Cochrane library from inception to September 2018 were systematically retrieved. The investigated outcomes included brachial-ankle pulse wave velocity (ba-PWV) and carotid-femoral PWV (cf-PWV) by using weighted mean differences (WMDs) and 95% confidence intervals (CIs) with the random-effects model. A total of 17 RCTs including 1,458 individuals were included. The summary results indicated no significant differences between ACEIs and control for ba-PWV and cf-PWV. Also, no significant differences between ACEI and control for ba-PWV and cf-PWV were observed in hypertensive patients, while the therapeutic effects of ACEI versus placebo showed statistically significant difference. Moreover, subgroup analysis indicated that the levels of ba-PWV were significantly associated if the study was conducted in Western countries, mean age <60.0 years, percentage male ≥60.0%, compared with ARBs, baseline PWV <10.0, and high-quality study. Furthermore, the significant levels of cf-PWV in patients who received ACEIs were observed when percentage male was ≥60.0% and the studies were of high-quality. Finally, no significant differences were observed between ACEIs and other antihypertensive drugs regarding the changes of systolic blood pressure (SBP) and diastolic blood pressure (DBP). The overall analysis suggested no significant differences between ACEIs and other antihypertensive drugs for ba-PWV and cf-PWV levels, whereas ACEIs versus placebo showed lower levels of ba-PWV and cf-PWV.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Rigidez Vascular/efeitos dos fármacos , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Velocidade da Onda de Pulso Carótido-Femoral , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
6.
Clin Interv Aging ; 14: 743-752, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118595

RESUMO

Objective: The aim of this study was to confirm the potential role of testosterone in hypertension and target organ damage (TOD) in hypertensive postmenopausal women. Methods: A matched group study was conducted. One hundred sixty-one hypertensive postmenopausal women between 45 and 65 years of age were enrolled as group 1. Another 161 age-matched hypertensive men were enrolled as group 2. Ambulatory blood pressure monitoring, echocardiographic imaging, vascular function, sex hormones and clinical characteristics were evaluated. Quantitative data were analyzed using independent Student's t-test and multiple regression analysis. Results: The mean and load level of blood pressure were lower in women than in men (P<0.05), except for the mean level and load of the nocturnal systolic blood pressure (SBP) (123.77±15.72 mmHg vs 126.35±15.64 mmHg, and 50.43±30.31% vs 55.35±28.51%, P>0.05). However, the carotid-femoral pulse wave velocity (cf-PWV) in women was higher than that in men (9.68±2.23 m/s vs 8.03±2.82 m/s, P<0.05). The ratio of the early diastolic mitral peak flow velocity to early diastolic mitral annular velocity (E/Em) was obviously impaired (13.06±3.53 vs 12.05±3.68, P<0.05) in women. Furthermore, in women, a positive correlation was found between testosterone and cf-PWV (γ=0.157, P=0.046), and Cf-PWV was positively related to the mean level of nighttime SBP (γ=0.210, P=0.008). Moreover, nocturnal SBP was a risk factor for E/Em (γ=0.156, P=0.048, P<0.05). Conclusion: Testosterone may play a role in the correlation between hypertension and TOD in hypertensive postmenopausal women. Clinical Trial number: This research study was registered under the ClinicalTrials.gov PRS Website (NCT03451747).


Assuntos
Hipertensão/complicações , Hipertensão/fisiopatologia , Pós-Menopausa/fisiologia , Testosterona/sangue , Idoso , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Estudos Transversais , Eletrocardiografia , Feminino , Hormônios Esteroides Gonadais/sangue , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de Risco
7.
J Cardiovasc Pharmacol Ther ; 24(5): 450-459, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31023080

RESUMO

BACKGROUND: Hypertension is a major cause of death and morbidity worldwide and is increasing in prevalence. The Renin-angiotensin system (RAS) is the most common mechanism involved in the pathophysiology of hypertension. Understanding the mechanism of the pathophysiologic processes will help direct potential therapeutic strategies to treat hypertension and improve cardiac function. Recently, a novel drug LCZ696 containing both an angiotensin receptor blocker valsartan and a neprilysin inhibitor (AHU377) has shown a promising effect on the treatment of hypertension. However, the effects of LCZ696 on the expression of main components of RAS, namely, angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1 R), angiotensin II type 2 receptor (AT2 R), and angiotensin (1-7) receptor/Mas receptor (MasR) remain unclear. The aim of the present study was to evaluate the effects of LCZ696 on the protective arms of RAS in the cardiac tissue when compared with valsartan under the equal inhibition of AT1 R. We hypothesized that the superior effects of LCZ696 may contribute to its greater effect on the RAS than valsartan. MATERIALS AND METHODS: Sixteen-week-old female spontaneously hypertensive rats (SHRs) were used in this study. Wistar-Kyoto (WKY) rats were used as controls. All rats were randomly divided into LCZ696 (n = 10), valsartan (n = 10), SHR (n = 10), and WKY (n = 10) groups under a 12-hour dark and 12-hour light cycle and provided with regular chow diet and water. The tail-cuff method was performed to measure blood pressure. Cardiac function was assessed by echocardiography. RESULTS: The blood pressure value was lower in LCZ696 than valsartan in SHR after 12 weeks of treatment. Further, LCZ696 inhibits the ACE and AT1 R protein expression in the cardiac of SHR and significantly upregulate the protective axis of RAS components, including ACE2, MasR, and AT2 R. Left ventricular AT2 R messenger RNA (mRNA) expression was higher in the LCZ696+SHR group compared with valsartan. In addition, real-time polymerase chain reaction analysis revealed that LCZ696 enhanced the mRNA expression of antihypertensive components AT2 R, ACE2, and MasR and decreased the expression of AT1 R. However, only AT2 R and ACE2 mRNA expressions have a statistical difference between the LCZ696 and valsartan groups. No difference was observed in the mRNA expression of ACE and MasR. The stronger positive signal of transforming growth factor ß in the left ventricle was inhibited in each administrated group compared with SHR groups. CONCLUSIONS: LCZ696 ameliorates the vasoconstrictor axis of the RAS AT1 R and stimulate the protective arm effectors, ACE2 and AT2 R, as well as reverses the compensatory upregulation of neuronal nitric oxide synthase and endothelial nitric oxide synthase in SHR. These findings suggest the mechanistic insight of the cardiac-protective and greater hypotensive effects of LCZ696.


Assuntos
Aminobutiratos/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Tetrazóis/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Compostos de Bifenilo , Modelos Animais de Doenças , Combinação de Medicamentos , Feminino , Fibrose , Regulação da Expressão Gênica , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Miócitos Cardíacos/metabolismo , Neprilisina/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sistema Renina-Angiotensina/genética , Transdução de Sinais , Valsartana , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-750298

RESUMO

@#Objective    To analyze the effect of loop-in-loop technique and annuloplasty ring for the treatment of mitral valve prolapse (MVP) under total thoracoscopy. Methods    Between May 2012 and May 2017, 21 patients with MVP underwent mitral valve repair in our hospital. There were 12 males and 9 females with a mean age of 50.90±9.66 years and the mean weight of 64.81±11.56 kg. Loop-in-loop artificial chordae tendonae reconstruction and mitral annuloplasty were performed through the right atrial-atrial septal incision under total thoracoscopy. The water test and transesophageal echocardiography were performed during the operation to evaluate the effect of mitral annuloplasty. Data of echocardiography and chest radiography were collected postoperatively one week, before discharge and after discharge. Results    All the operations were successful without re-valvupoplasty or valve replacement, conversion to median thoracotomy, malignant arrhythmia, perioperative death or wound infection. Among them, 10 patients underwent tricuspid valvuloplasty, 1 patient underwent tricuspid valvuloplasty plus radiofrequency ablation simultaneously. The mean cardiopulmonary bypass time was 255.57±37.24 minutes, aortic occlusion time was 162.24±19.61 minutes, the number of loop was 2–5 (3.29±0.78), the size of ring was 28–34 (31.11±1.88) mm, ventilator assistance time was 19.43±14.68 hours, ICU time was 58.45±24.60 hours and postoperative hospital stay was 12.28±3.61 days. Transthoracic echocardiography was re-examined postoperatively. Mild-mitral regurgitation was found in 3 patients. Warfarin anticoagulant therapy was given orally for 6 months postoperatively. The patients were followed up regularly for 2–51 months at 1, 3, 6 and 12 months postoperatively. Left ventricular end-diastolic diameter (LVEDD) was 45.06±2.96 mm, left ventricular end-diastolic volume 108.11±17.09 mL, left atrial diameter (LAD) 35.56±6.93 mm and cardiothoracic ratio 0.53±0.13 at discharge which were significantly smaller than those at admission (P<0.05). Pulmonary artery pressure was 19.22±6.38 mm Hg which was significantly lower than that at admission (P<0.05), but left ventricular ejection fraction (62.33%±4.00%) had no significant change (P>0.05). The LAD and LVEDD were significantly smaller than those before operation, and the cardiac function improved to some extent during the follow-up. No new mitral valve prolapse, increased regurgitation, infective endocarditis, thromboembolism or anticoagulation-related complications were found during the follow-up. Conclusion    Loop-in-loop artificial chordae tendon implantation combined with mitral annuloplasty is a safe and effective method for MVP under total thoracoscopy with minimal trauma, satisfactory cosmetic effect, and good early- and medium-term results. It is worth of popularizing. However, the operation time needs to be further shortened, and its long-term clinical effect needs further follow-up and other researches to confirm.

9.
Chin Med J (Engl) ; 131(5): 516-526, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29483384

RESUMO

BACKGROUND: Postmenopausal women with metabolic syndrome (MetS) have increased cardiovascular morbidity and left ventricular diastolic dysfunction (LVDD). The various protective effects of astragalus membranaceus (AM) have been described in previous studies. Therefore, this study aimed to evaluate the effects of different doses of AM on diastolic function in postmenopausal hypertensive women with MetS. METHODS: This was a prospective, randomized controlled study. The postmenopausal hypertensive patients with MetS were enrolled from Lanzhou University Second Hospital from March 2014 to April 2015. Patients were divided into three groups: control group (received conventional medical treatment), AM Group 1 (received AM capsules at 5 g/d additionally), and AM Group 2 (received AM capsules at 10 g/d additionally). Echocardiographic and clinical characteristics were evaluated before and 12 months after treatment. Quantitative data were analyzed using unpaired t-test, analysis of variance, and multiple linear regression analysis. RESULTS: A total of 154 patients were subjected to final analysis. In the AM Group 2, significant improvements were noted in diastolic function 12 months after treatment than those of the control group, including the early diastolic mitral annular velocity (E'; 0.065 ± 0.007 m/s vs. 0.061 ± 0.008 m/s, P = 0.014), the ratio of the early diastolic mitral peak flow velocity to the late diastolic mitral peak flow velocity (E/A; 0.81 ± 0.05 vs. 0.80 ± 0.06, P = 0.012), the ratio of E' to the late diastolic mitral annular velocity (E'/A'; 0.56 ± 0.12 vs. 0.51 ± 0.13, P = 0.048), and the ratio of the early diastolic mitral peak flow velocity (E) to E' (E/E'; 10.70 ± 1.30 vs. 11.37 ± 1.73, P = 0.031). After treatment, E/E' (10.70 ± 1.30 vs. 11.24 ± 1.56, P = 0.021), deceleration time (DT; 261.49 ± 44.41 ms vs. 268.74 ± 53.87 ms, P = 0.046), and E'/A' (0.56 ± 0.12 vs. 0.52 ± 0.13, P = 0.019) values improved more significantly than those of AM Group 2 before treatment. Besides, waist circumference was positively correlated with E' (r = 0.472; P = 0.003) and E'/A' (r = 0.321; P = 0.047). In addition, the waist-to-hip ratio was a significant predictor of DT (r = 0.276; P = 0.041), E' (r = -0.590; P < 0.001), E/E' (r = 0.454; P = 0.004), and E'/A' (r = -0.377; P = 0.018). CONCLUSIONS: Conventional medical plus AM therapy improved diastolic function. Moreover, WC and WHR might be risk factors for LVDD. CHINESE CLINICAL TRIAL REGISTER: ChiCTR-TRC-11001747. http://www.chictr.org.cn/showprojen.aspx?proj=7798.


Assuntos
Astragalus propinquus/química , Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Pós-Menopausa/efeitos dos fármacos , Estudos Prospectivos , Fatores de Risco
10.
J Cardiovasc Pharmacol Ther ; 22(5): 447-457, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28793821

RESUMO

LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, has been demonstrated to have greater advantages in the treatment of heart failure compared with angiotensin-converting enzyme inhibitors, enalapril, or angiotensin receptor blockers (ARBs). However, studies that compared the efficacy and safety of LCZ696 against valsartan in patients with hypertension are limited. To provide further evidence for the benefits of LCZ696 and to make this assessment, a meta-analysis of randomized controlled trials (RCTs) was performed. The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, PubMed, and ClinicalTrials.gov were searched for RCTs. Twelve studies involving 3816 patients were eligible for inclusion. Seven studies compared LCZ696 with valsartan, and 5 studies compared LCZ696 with olmesartan. LCZ696 showed a significantly greater reduction in systolic blood pressure (BP; mean difference [MD] = -5.43 mm Hg; 95% confidence interval [CI]: -6.36 to -4.49 mm Hg; P < .001), diastolic BP (MD = -2.34 mm Hg; 95% CI: -2.67 to -2.01 mm Hg; P < .001), 24-hour ambulatory systolic BP (MD = -3.57 mm Hg, 95% CI: -4.29 to -2.85 mm Hg; P < .001), and 24-hour ambulatory diastolic BP (MD = -1.32 mm Hg, 95% CI: -1.77 to -0.78 mm Hg; P < .001) from the baseline than ARBs. LCZ696 was more effective in reducing BP (odds ratio [OR] = 5.34; 95% CI: 4.49-6.36; P < .01) and had a higher rate of BP control compared with ARBs (OR = 1.52; 95% CI: 1.37-1.69; P < .01). LCZ696 had no difference in the incidence of adverse events (OR = 1.05; 95% CI: 0.94-1.18; P = .38) or serious adverse events (OR = 0.80; 95% CI: 0.51-1.24; P = .31) compared to ARBs. This meta-analysis revealed that LCZ696 has a greater antihypertensive efficacy and an equal tolerability profile.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Hipertensão/tratamento farmacológico , Tetrazóis/uso terapêutico , Aminobutiratos/efeitos adversos , Compostos de Bifenilo , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Combinação de Medicamentos , Humanos , Hipertensão/fisiopatologia , Tetrazóis/efeitos adversos , Valsartana
11.
Gynecol Endocrinol ; 32(9): 685-689, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27176003

RESUMO

Postmenopausal hypertensive is associated with estrogen deficiency. This meta-analysis was performed to assess the efficacy and safety of drospirenone combined with 17-ß-estradiol (DRSP/E2) in postmenopausal hypertensive women. A systemic literature search of PubMed, Embase, Cochrane Library, Web of Science (up to Oct. 2015) was performed. Studies were screened independently by two researchers according to the inclusion and exclusion criteria which included only the randomized controlled trials (RCT) about the drospirenone with 17-ß-estradiol for postmenopausal women with hypertension. The methodological quality was evaluated by Cochrane handbook 5.1.0 and meta-analysis was conducted using RevMan 5.3.0 software. Five randomized controlled trials involved 1121 patients who met the eligibility criteria. Overall, DRSP/E2 group was superior in reducing clinical blood pressure (BP) and 24-h mean BP. There was no significant change in potassium levels on DRSP/E2 group versus control group, suggesting probability potassium sparing effect of this hormone therapy. The incidences of adverse events were low and similar. The current evidences indicate that DRSP 3 mg/E2 2 mg can significantly lower both systolic and diastolic blood pressure in postmenopausal hypertensive women.


Assuntos
Androstenos/farmacologia , Quimioterapia Combinada , Estradiol/farmacologia , Hipertensão/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Pós-Menopausa/efeitos dos fármacos , Androstenos/administração & dosagem , Estradiol/administração & dosagem , Feminino , Humanos , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem
12.
Zhongguo Zhong Yao Za Zhi ; 41(21): 4051-4059, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-28929695

RESUMO

To explore the effect of Mongolia Astragali Radix produced in Longxi of Gansu province in protecting cardiac and nephritic functions of patients of essential hypertension(EH) with metabolic syndrome(MetS). A total of two hundred and twenty-six EH patients with MetS aged above 18 were selected. Patients were randomly divided to control group(adopted conventional medical treatment), Astragali Radix group 1(added Astragali Radix capsules 10 g•d⁻¹ besides conventional medical treatment) and Astragali Radix group 2(added Astragali Radix capsules 5 g•d⁻¹ besides conventional medical treatment). Cardiac anatomy structure, cardiac systolic function and diastolic function were measured by M-mode echocardiography, two-dimensional echocardiography, Doppler echocardiographic determination and tissue Doppler imaging. The level of microalbuminuria(MAU) was evaluated by radioimmunoassay. In addition, the estimated glomerular filtration rate(eGFR) was calculated by modification of diet in renal disease (MDRD) formulas. The changes of relevant indicators for cardiac and nephritic functions before and after treatment were compared during the 12-month follow-up. The study protocol was registered at the website of Chinese clinical trial register and approved by the ethics committee of second hospital of Lanzhou university. Each patient was required to sign an informed consent. SPSS software was used for statistical analysis. According to the result, compare with before treatment, the three groups show no difference in efficacy of metablic indicators. Left ventricular end-systolic volume (ESV) and left ventricular end-systolic dimension (LVESd) of all patients were improved after treatment. However, there was no significant difference among the three groups. After the addition of Astragali Radix, the mitral flow velocity(Vp) of patients was improved to some extent(P<0.05). However, there was no significant difference among the three groups. Astragali Radix had a significant effect in reducing the MAU(P<0.05). Moreover, the MAU level of patients in Astragali Radix group 1 decreased more significantly than the other groups(P<0.05). Compared with conventional therapy, Astragali Radix combined with conventional therapy could improve cardiac structure, left ventricular systolic function, left ventricular diastolic function, and reduce the MAU to a certain extent in EH patients with MetS. Moreover, the effects of high-dose Astragali Radix are better than that of the low-dose Astragali Radix. However, the effect of Astragali Radix on EH patients with MetS shall be further observed to confirm its efficacy.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Astrágalo , Pressão Sanguínea , Taxa de Filtração Glomerular , Humanos , Função Ventricular Esquerda
13.
Zhongguo Zhong Yao Za Zhi ; 40(21): 4245-50, 2015 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-27071265

RESUMO

To study the expression of angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang) 1-7 specific receptor Mas protain in renal blood vessels of metabolic syndrome ( MS) rats and its anti-oxidative effect. A total of 80 male SD rats were divided into four groups: the normal control group (NC, the same volume of normal saline), the MS group (high fat diet), the MS + Astragali Radix group (MS + HQ, 6 g x kg(-1) x d(-1) in gavage) and the MS + Valsartan group (MS + XST, 30 mg x kg(-1) x d(-1) in gavage). After four weeks of intervention, their general indexes, biochemical indexes and blood pressure were measured; plasma and renal tissue Ang II, malondialdehyde (MDA) and superoxide demutase (SOD) levels were measured with radioimmunoassay. The protein expressions of Mas receptor, AT1R, ACE and ACE2 were detected by western blot analysis. According to the result, compared with the NC group, the MS group and the MS + HQ group showed significant increases in systolic and diastolic pressures, body weight, fasting glucose, fasting insulin, triglycerides, free fatty acid and Ang II level of MS rats (P < 0.05). The MS + XST group showed notable decreases in systolic and diastolic pressures than that of the MS group. The MS group showed significant increases in the SOD activity and NO level and decrease in the MDA level after being intervened with Astragali Radix. ACE and AT1R protein expressions in renal tissues of the MS group were higher than that in the NC group, but with lower ACE2 and -Mas receptor expressions (all P < 0.05). Compared with the MS group, the MS + HQ group showed significant increase in Mas receptor expression in renal tissues, whereas the MS + XST group showed notable decrease in AT1R (all P < 0.05). In conclusion, Astragali Radix can increase the Mas receptor expressions in renal tissues, decrease ACE expression and change local Ang II, MDA, NO and SOD in kidneys, so as to protect early damages in renal tissues.


Assuntos
Astrágalo/química , Medicamentos de Ervas Chinesas/administração & dosagem , Síndrome Metabólica/tratamento farmacológico , Peptidil Dipeptidase A/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Angiotensina I/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/lesões , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/genética , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/efeitos dos fármacos
14.
Endocrine ; 43(3): 548-63, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23371816

RESUMO

The prevalence of metabolic syndrome (MS) has been on the rise over the past few decades, and this is associated with an increased incidence of target organ damage such as left ventricular hypertrophy (LVH). This meta-analysis aims to evaluate the features of LVH in MS patients with or without high blood pressure (BP). PubMed, Cochrane Library, Embase, Science Citation Index, and China Biology Medicine Disc, WanFang data, China National Knowledge Infrastructure database, and VIP were searched. Cross-sectional studies which directly compared LVH in hypertensive patients with MS and those with hypertension alone were identified. The following parameters were analyzed: systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular mass/height(2.7) (LVM/h(2.7)), interventricular septum thickness (IVSt), left ventricular end-diastolic diameter (LVEDd), left ventricular posterior wall (LVPW), ratio of early to late diastolic peak flow velocity (E/A), and relative wall thickness (RWT). Data were extracted and analyzed by Cochrane Collaboration's RevMan 5.0 software. 14 studies involving 5,994 patients were included. In four studies, MS patients with comparable level of BP had higher SBP (mmHg) [Mean Difference (MD) = 2.28, 95 % confidence intervals (CI): -0.58 to 5.13], DBP (mmHg) (MD = 1.32, 95 % CI: -0.23 to 2.87), LVM (g) (MD = 42.10, 95 % CI: 6.92-77.28), LVMI (g/m(2)) (MD = 8.93, 95 % CI: 5.29-12.57), LVM/h(2.7) (g/m(2.7)) (MD = 5.40, 95 % CI: 2.51-8.29), IVSt (mm) (MD = 0.49, 95 % CI: 0.28-0.71), LVEDd (mm) (MD = 1.04, 95 % CI: -1.10 to 3.18), LVPW (mm) (MD = 0.75, 95 % CI: 0.13-1.37), RWT (MD = 0.06, 95 % CI: -0.00 to 0.12), and lower E/A (MD = -0.08, 95 % CI: -0.18 to 0.02) when compared to the patients with hypertension alone. In other ten studies, the hypertensive patients with MS exhibited higher levels of SBP (mmHg) (MD = 4.67, 95 % CI: 2.72-6.62), DBP (mmHg) (MD = 2.03,95 % CI: 1.40-2.65), LVM (g) (MD = 24.79, 95 % CI: 20.21-29.36), LVMI(g/m(2)) (MD = 9.22, 95 % CI: 2.81-15.64), LVM/h(2.7) (g/m(2.7)) (MD = 5.97, 95 % CI: 4.14-7.80), IVSt (mm) (MD = 0.63, 95 % CI: 0.58-0.69), LVEDd (mm) (MD = 1.11, 95 % CI: 0.42-1.80), LVPW (mm) (MD = 0.63, 95 % CI: 0.31-0.94), RWT (MD = 0.02, 95 % CI: 0.01-0.03), as compared to patients with hypertension alone (P < 0.05). In addition, the MS patients combining with hypertension showed a lower E/A (MD = -0.07, 95 % CI: -0.10 to -0.04) when compared to those with hypertension alone. This study suggests that MS plays an important role in the development of LVH. MS seems to amplify hypertension-related cardiac changes. Furthermore, MS combining with higher level of BP will aggravate LVH and damage the diastolic function of left ventricle.


Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Síndrome Metabólica/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Coração/fisiopatologia , Humanos , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/complicações , Síndrome Metabólica/complicações
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