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1.
Medicine (Baltimore) ; 98(52): e18295, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876705

RESUMO

RATIONALE: 3-Methoxyphencyclidine (3-MeO-PCP) is a new psychoactive substance derived from phencyclidine. Although it can lead to severe intoxications, the main manifestations and optimal management have not been well characterized. Here, we report 2 cases of 3-MeO-PCP intoxication in the same patient, and summarize the manifestations of this intoxication reported in literature. PATIENT CONCERNS: A 17-year-old male purchased a bag of 3-MeO-PCP on the Internet but took an oral dose (200 mg) that corresponds to the less active isomer 4-MeO-PCP. He developed high blood pressure (158/131 mm Hg), tachycardia (100 bpm), and neurological manifestations (confusion, hypertonia, nystagmus, and then agitation). A maculopapular rash appeared, although this may have been related to the administration of midazolam. Hyperlactatemia (2.6 mmol/L) was the main laboratory finding. Seven days later, he returned to the emergency department after sniffing 50 mg of 3-MeO-PCP. High blood pressure, tachycardia, and neurological manifestations (psychomotor impairment and dysarthria) were present but less severe than after the first intoxication. DIAGNOSIS: In the first intoxication, the blood and urine 3-MeO-PCP concentrations were, respectively, 71.1 ng/mL and 706.9 ng/mL. Conventional toxicity tests were all negative. In the second intoxication, biological samples were not available. INTERVENTIONS: In the first intoxication, treatment consisted of intravenous hydration and midazolam. The patient was transferred to an intensive care unit for monitoring. After the second intoxication, he was monitored for 12 hours. OUTCOMES: The patient's condition improved quickly in both cases. LESSONS: These cases provide additional information on the manifestations of 3-MeO-PCP intoxication. These manifestations are mainly cardiovascular (high blood pressure, tachycardia) and neurological. The fact that second (50 mg) intoxication was less severe than the first (200 mg) is suggestive of a dose-effect relationship for 3-MeO-PCP. The first case also emphasizes the risk of dosing errors caused by the similarity between the names "3-MeO-PCP" and "4-MeO-PCP."


Assuntos
Drogas Desenhadas/envenenamento , Fenciclidina/análogos & derivados , Adolescente , Humanos , Hipertensão/induzido quimicamente , Masculino , Fenciclidina/sangue , Fenciclidina/envenenamento , Fenciclidina/urina , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Taquicardia/induzido quimicamente
2.
Presse Med ; 48(11 Pt 1): 1269-1283, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31757732

RESUMO

Hypertension is a major risk factor for cardiovascular diseases. Because of the high frequency of hormonal contraceptives use, assessing their side effects is an important public health issue. In this perspective, we conducted a review of the risk of hypertension associated with the use of hormonal contraceptives, either combined estrogen-progestin or only progestin. The use of combined hormonal contraceptives, regardless of its type and route of administration, is associated with a slight increase in blood pressure, both systolic and diastolic blood pressures. The frequency of onset of hypertension in women who use combined hormonal contraception is between 0.6% and 8.5%. Progestin-only contraception seems safe with respect to the risk of hypertension. It is therefore important to remember that the use of combined hormonal contraception is contra-indicated in hypertensive women, even well controlled. Finally, we propose a prescription assistance algorithm according to the recommendations of an expert panel. It should be remembered that taking blood pressure at each contraceptive consultation (initial and follow-up) is essential.


Assuntos
Anticoncepção/efeitos adversos , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Hipertensão/induzido quimicamente , Progestinas/efeitos adversos , Adolescente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Determinação da Pressão Arterial , Feminino , Humanos , Pessoa de Meia-Idade , Progestinas/administração & dosagem , Fatores de Risco , Adulto Jovem
3.
Cardiovasc Hematol Agents Med Chem ; 17(2): 135-143, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31589128

RESUMO

BACKGROUND: Matricaria pubescens is a medicinal plant from North Africa. This plant is widely used in alternative medicine as a remedy against rheumatism, inflammation, diabetes and hypertension. AIM: The aim of the study was to evaluate the possible antihypertensive and vasodilator activity of the aqueous extract of Matricaria pubescens (M. pubescens). MATERIAL AND METHODS: In the current study, the aqueous extract of the aerial parts of M. pubescens (AEMP) was prepared and its antihypertensive activity was examined in N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. RESULTS: The results indicated that AEMP reduced the systolic, diastolic, mean arterial blood pressure in hypertensive rats but not in normotensive rats. The data revealed that AEMP exhibits its antihypertensive effect through vasorelaxant activity. More interestingly, this study approved that the vasorelaxant capacity of AEMP seems to be mediated through vascular cyclooxygenase pathway, the opening of K+ channels and sGC-cGMP induction pathway. CONCLUSION: The study illustrates the beneficial action of M. pubescens as an antihypertensive agent.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Matricaria/química , Extratos Vegetais/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Masculino , NG-Nitroarginina Metil Éster/efeitos adversos , Extratos Vegetais/química , Ratos Wistar , Vasodilatadores/química
4.
Cancer Invest ; 37(9): 478-488, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31557062

RESUMO

Hypertension is associated with enzalutamide in the treatment of prostate cancer. We performed a meta-analysis of randomized clinical trials to determine the risk of hypertension. Databases including Pubmed and Google scholar were searched to identify randomized clinical trials with enzalutamide. A total of seven studies including 7347 patients were selected. The overall incidences of all-grade and high-grade hypertension were 11.9% (95%% CI: 8.8-16.0%) and 4.9% (95%% CI: 3.5-6.8%) respectively, with a relative risk of 2.82 (95%% CI: 2.34-3.38, p < 0.001) for all-grade and 2.27 (95%% CI: 1.73-2.96, p < 0.001) for high-grade. There was a significant risk of developing hypertension with enzalutamide.


Assuntos
Hipertensão/epidemiologia , Feniltioidantoína/análogos & derivados , Neoplasias da Próstata/tratamento farmacológico , Humanos , Hipertensão/induzido quimicamente , Incidência , Masculino , Feniltioidantoína/efeitos adversos , Feniltioidantoína/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Rev Med Suisse ; 15(662): 1625-1628, 2019 Sep 11.
Artigo em Francês | MEDLINE | ID: mdl-31508914

RESUMO

The salt sensitivity of the blood pressure (SSBP) is defined as a rise or fall in blood pressure induced by a change in sodium intake. There is an interindividual variation and no strong diagnostic criteria exist to date. The SSBP may lead to underestimation of the beneficial effect of sodium restriction in some patients in meta-analyzes. High sodium intake in salt sensitive patients results in an increase in the prevalence of hypertension and target organ damage. The etiology seems to be a failure of one or more natriuretic mechanisms. Some environmental, genetic and epidemiological factors increase its susceptibility. Per se, SSBP cannot be treated, but its identification may help in preventing hypertension and adapt the treatment in some populations.


Assuntos
Variação Biológica Individual , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Cloreto de Sódio na Dieta/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/diagnóstico
6.
Life Sci ; 235: 116862, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31513814

RESUMO

Dysregulation of miR-29 has been revealed in multiple diseases, but its role in the development of hypertension and vascular endothelial dysfunction has not been defined. Here, we found that, compared with the wild-type (WT) Wistar rats, miR-29b was robustly upregulated in spontaneously hypertensive rats (SHRs), while CTRP6 was distinctly downregulated. There were two miRNA-responding-elements (MREs) for miR-29 in the 3'-UTR of CTRP6 mRNA, and the luciferase activity assay revealed that miR-29b directly targeted CTRP6 mRNA. Intraventricular injection was applied to deliver the miR-29b mimic or miR-29b inhibitor (4 mg/kg) into SHRs once two weeks from 10th week. Downregulation of miR-29b could increase serum CTRP6 content in SHRs, decrease the arterial systolic pressure, reduce serum concentrations of Ang II and ET-1, and enhance serum NO content. Meanwhile, we demonstrated that inhibition of miR-29b increased the phosphorylation of ERK1/2 to activate PPARγ, an inducer of Ang II. Finally, miR-29b expression was manipulated in, and CTRP6 recombinant protein was applied to incubate with the primary aortic endothelial cells. Inhibition of miR-29b increased CTRP6 expression, improved cell proliferation and migration, suppressed secretion of Ang II and ET-1, and decreased ROS accumulation and LDH release, displaying a similar effect to the CTRP6 recombinant protein. Moreover, the CTRP6 recombinant protein could antagonize the suppressive effect of miR-29b on activation of the ERK/PPARγ axis and function of aortic endothelial cells. In conclusion, miR-29b antagonism can alleviate Ang II-induced hypertension and vascular endothelial dysfunction through activating the CTRP6/ERK/PPARγ axis.


Assuntos
Angiotensina II/efeitos adversos , Células Endoteliais/efeitos dos fármacos , Hipertensão/genética , Hipertensão/prevenção & controle , MicroRNAs/antagonistas & inibidores , Adipocinas/sangue , Angiotensina II/sangue , Animais , Pressão Sanguínea/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Regulação para Baixo/efeitos dos fármacos , Endotelina-1/sangue , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , L-Lactato Desidrogenase/metabolismo , Masculino , MicroRNAs/agonistas , MicroRNAs/biossíntese , MicroRNAs/genética , Óxido Nítrico/sangue , Fosforilação/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
7.
Chemosphere ; 237: 124510, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549641

RESUMO

Several studies have demonstrated associations between short-term exposure to particulate matter (PM) and blood pressure (BP) among various adults groups, but evidence in children and adolescents is still rare. In 2016, a cross-sectional survey was conducted among 194 104 participants aged 6-17 years in Suzhou, China. Daily concentrations of particulate matters with an aerodynamic diameter of ≤10 µg/m3 (PM10) and aerodynamic diameter ≤2.5 µg/m3 (PM2.5) on 0-6 days preceding BP examination were collected from nearby air monitoring stations. Using generalized linear mixed-effects models, short-term effects of PM on personal BP were estimated. A 10 µg/m3 increment in the 0-6 day mean of PM2.5 was significantly associated with elevation of 0.20 mmHg [95% confidence interval (95% CI) 0.16-0.23] in systolic BP (SBP), 0.49 mmHg (95% CI 0.45-0.53) in diastolic BP (DBP), respectively. Similarly, 0.14 mmHg (95% CI 0.12-0.16) higher SBP and 0.32 mmHg (95% CI 0.30-0.34) higher DBP were found for each 10 µg/m3 increase in 0-6 day mean of PM10. More apparent associations were observed in females than in males. Odds ratio (95%CI) of for PM2.5 exposure at 0-6 d mean was 1.06 (1.03-1.08) in females, while it was 1.01 (0.99-1.03) in males. Participants with young ages, underweight and obesity were also associated with increased susceptibility to PM-induced BP effects. Short-term exposure in PM was significantly associated with elevated BP in children, indicating a need to control PM levels and protect children from PM exposure in China.


Assuntos
Poluição do Ar/estatística & dados numéricos , Pressão Sanguínea , Exposição Ambiental/estatística & dados numéricos , Material Particulado/análise , Adolescente , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Criança , China , Cidades , Estudos Transversais , Feminino , Humanos , Hipertensão/induzido quimicamente , Modelos Lineares , Masculino , Obesidade , Razão de Chances , Rios , Adulto Jovem
9.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(9): 919-924, 2019 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-31474074

RESUMO

Objective: To investigate the effect of long-term exposure of nitrogen dioxide on the incidence of hypertension. Methods: From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow-up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self-report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO2 during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO2 exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO2 exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results: The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m(2). During an average follow-up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) µg/m(3). After adjusting for age, sex, BMI, family history of hypertension, socio-economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 µg/m(3) increase of NO2 was 1.21 (95%CI: 1.18-1.25). Compared with residents aged 60 years and over (HR=1.19, 95%CI: 1.14-1.26), former and current smoking (HR=1.20, 95%CI: 1.14-1.25), and high-frequency fruit consumption (HR=1.17, 95%CI: 1.13-1.21), residents younger than 60 years (HR=1.28, 95%CI: 1.25-1.32), non-smoker (HR=1.23, 95%CI: 1.19-1.27), and low-frequency fruit consumption (HR=1.27, 95%CI: 1.20-1.35) had stronger interaction effect with NO2 (all P values for interaction<0.05). Conclusion: NO2 exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low-frequency fruit consumption.


Assuntos
Poluentes Atmosféricos , Exposição Ambiental , Hipertensão , Dióxido de Nitrogênio , Adulto , Poluentes Atmosféricos/toxicidade , China , Estudos de Coortes , Seguimentos , Humanos , Hipertensão/induzido quimicamente , Pessoa de Meia-Idade , Dióxido de Nitrogênio/toxicidade , Estudos Retrospectivos
10.
Medicine (Baltimore) ; 98(33): e16838, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415406

RESUMO

RATIONALE: Hypertrophic cardiomyopathy (HCM) is a heterogeneous, usually familial disorder of heart muscle. The hypertrophic form of cardiomyopathy is frequently genetic, or as part of several neuromuscular disorders. In neonates, especially prematurity, HCM could also be secondary to corticosteroid treatment. PATIENT CONCERNS: We reported here a 34 weeks gestational age preterm infant presented with profound cardiomegaly after multiple doses of hydrocortisone used to treat blood pressure instability associated with septic shock and persistent pulmonary hypertension (PPHN). DIAGNOSIS: Patient presented auscultation of a grade III/IV harsh systolic ejection murmur from day 14, which was absent before. Profound cardiomegaly was indicated at chest film at day 30. Echocardiography showed severe thickening of the IVS (13.8 mm, z score = 8.29) and mild thickening of the posterior left ventricular wall (LVPW, 6 mm). INTERVENTIONS: Propranolol and captopril were started along with supportive care. The patient was also admitted to NICU for further treatment with 24-hour Holter electrocardiographic monitoring. OUTCOMES: A reversible course was observed without left ventricular outflow tract obstruction nor arrhythmias within 4 weeks. LESSONS: The risk/benefit ratio must be carefully considered when corticosteroids are used in prematurity. Monitors such as echocardiography and electrocardiograph should be conducted in order to guide cardiovascular management. Systematic surveys of the incidence of cardiac complications in a larger population of preterm infant treated with corticosteroid are needed in the future.


Assuntos
Cardiomiopatia Hipertrófica/induzido quimicamente , Hidrocortisona/efeitos adversos , Hipertensão/induzido quimicamente , Doenças do Prematuro/tratamento farmacológico , Síndrome da Persistência do Padrão de Circulação Fetal/tratamento farmacológico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino
11.
Environ Pollut ; 254(Pt A): 112971, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31394346

RESUMO

The effects of exposure to some environmental chemicals on blood pressure have been determined, but the association between non-occupational exposure to perfluoroalkyl substances (PFASs) and blood pressure in adolescents remains unknown. The association between blood pressure and PFAS concentrations was studied by analysing data from 2251 participants filtered from the population enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2012. After adjusting for age, sex, race, BMI, cotinine level, dietary intake of calcium, caloric intake, sodium consumption, potassium consumption and sampling year, we estimated the coefficients (betas) and 95% confidence intervals (CIs) for the relationship between PFAS concentrations and blood pressure with multiple linear regression models. Potential non-linear relationships were assessed with restricted cubic spline models. Blood levels of perfluorooctane sulfonic acid (PFOS) had a strong positive association with diastolic blood pressure (DBP) in adolescents in the linear model, while the result was not significant in the non-linear model. No significant association was observed between the concentration of any other PFASs and blood pressure. According to the fully adjusted linear regression model (P = 0.041), the mean DBP values in boys in the higher PFOS quintile were 2.70% greater than the mean DBP values of boys in the lowest PFOS quintile. Furthermore, serum PFOS concentrations predominantly affected blood pressure in male adolescents compared with female adolescents. These results provide epidemiological evidence of PFOS-related increases in DBP. Further research is needed to address related issues.


Assuntos
Ácidos Alcanossulfônicos/sangue , Pressão Sanguínea/efeitos dos fármacos , Fluorcarbonetos/sangue , Hipertensão/induzido quimicamente , Adolescente , Cálcio/metabolismo , Cotinina/urina , Feminino , Humanos , Modelos Lineares , Masculino , Análise Multivariada , Inquéritos Nutricionais , Potássio/metabolismo , Fatores Sexuais , Sódio/metabolismo
12.
Life Sci ; 234: 116753, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419445

RESUMO

AIMS: Hypertension is a global disease that has been combating the world health for ages. Peristrophe roxburghiana (PR) is used in traditional medicine to treat hypertension and other ailments. The present study examined phytochemical constituents, antioxidant activities and GC-MS analysis of extracts of PR leaf and also evaluated their anti-hypertensive and anti-lipidemic effects in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHODS: Wistar rats were grouped into two groups: control and hypertensive. Hypertension was induced in the hypertensive group by oral gavage of 60 mg/kg b.w of L-NAME for 3 weeks. After induction, the hypertensive group was randomly sub-grouped into hypertensive, hypertensive treated and hypertensive untreated groups. These were orally gavaged respectively with 60 mg/kg b.w of L-NAME, 60 mg/kg b.w/day of L-NAME +200 mg/kg b.w of different extracts of PR (aqueous, ethanolic and methanolic extracts) and 60 mg/kg b.w of L-NAME +20 mg/kg b.w ramipril for 3 weeks. The blood pressure was measured by tail-cuff method at the third and sixth weeks. KEY FINDINGS: The results showed that the extracts of PR significantly decrease blood pressure, pro-atherogenic lipids and atherogenic ratios in L-NAME hypertensive rats. White blood cells count, neutrophil count and creatinine level were also effectively decreased by the extracts. Furthermore, the extracts increase serum nitric oxide (NO) level, anti-atherogenic lipid, glutathione level, lymphocyte and platelet count in the rats. SIGNIFICANCE: Extracts of PR leaf decrease blood pressure and increase NO level in L-NAME hypertensive rats and also corrected the hyperlipidemia and inflammatory response arising from the reduction in NO bioavailability.


Assuntos
Acanthaceae/química , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Hipolipemiantes/química , Lipídeos/sangue , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Extratos Vegetais/química , Folhas de Planta/química , Ratos Wistar
13.
Kidney Blood Press Res ; 44(4): 792-809, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430751

RESUMO

OBJECTIVE: We evaluated the hypothesis that the development of renal dysfunction and congestive heart failure (CHF) caused by volume overload in rats with angiotensin II (ANG II)-dependent hypertension is associated with altered renal vascular responsiveness to ANG II and to epoxyeicosatrienoic acids (EETs). METHODS: Ren-2 transgenic rats (TGRs) were used as a model of ANG II-dependent hypertension. CHF was induced by volume overload achieved by the creation of the aorto-caval fistula (ACF). Renal blood flow (RBF) responses were determined to renal arterial administration of ANG II, native 11,12-EET, an analog of 14,15-EETs (EET-A), norepinephrine (NE), acetylcholine (Ach) and bradykinin (Bk) in healthy (i.e., sham-operated) TGR and ACF TGR (5 weeks after ACF creation). RESULTS: Selective intrarenal administration of neither vasoactive drug altered mean arterial pressure in any group. Administration of ANG II caused greater decreases in RBF in ACF TGR than in sham-operated TGR, whereas after administration of NE the respective decreases were comparable in the 2 groups. Administration of Ach and Bk elicited significantly higher RBF increases in ACF TGR as compared with sham-operated TGR. In contrast, administration of 11,12-EET and EET-A caused significantly smaller RBF increases in ACF TGR than in sham-operated TGR. CONCLUSION: The findings show that 5 weeks after creation of ACF, the TGR exhibit exaggerated renal vasoconstrictor responses to ANG II and reduced renal vasodilatory responses to EETs, suggesting that both these alterations might play an important role in the development of renal dysfunction in this model of CHF.


Assuntos
Angiotensina II/efeitos adversos , Insuficiência Cardíaca/complicações , Hipertensão/induzido quimicamente , Circulação Renal/efeitos dos fármacos , Vasoconstritores/farmacologia , Animais , Fístula Artério-Arterial/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Hipertensão/complicações , Artéria Pulmonar/anormalidades , Artéria Pulmonar/fisiopatologia , Ratos , Ratos Transgênicos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
14.
Hypertension ; 74(4): 910-920, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31422690

RESUMO

Hypertension is associated with increased sympathetic activity. A component of this sympathoexcitation may be driven by increased signaling from sensory endings from the heart to the autonomic control areas in the brain. This pathway mediates the so-called cardiac sympathetic afferent reflex, which is also activated by coronary ischemia or other nociceptive stimuli in the heart. The cardiac sympathetic afferent reflex has been shown to be enhanced in the heart failure state and in renal hypertension. However, little is known about its role in the development or progression of hypertension or the phenotype of the sensory endings involved. To investigate this, we used the selective afferent neurotoxin, resiniferatoxin (RTX) to chronically abolish the cardiac sympathetic afferent reflex in 2 models of hypertension; the spontaneous hypertensive rats (SHRs) and AngII (angiotensin II) infusion (240 ng/kg per min). Blood pressure (BP) was measured in conscious animals for 2 to 8 weeks post-RTX. Epidural application of RTX to the T1-T4 spinal segments prevented the further BP increase in 8-week-old SHR and lowered BP in 16-week-old SHR. RTX did not affect BP in Wistar-Kyoto normotensive rats nor in AngII-infused rats. Epicardial application of RTX (50 µg/mL) in 4-week-old SHR prevented the BP increase whereas this treatment does not lower BP in 16-week-old SHR. When RTX was administered into the L2-L5 spinal segments of 16-week-old SHR, no change in BP was observed. These findings indicate that signaling via thoracic afferent nerve fibers may contribute to the hypertension phenotype in the SHR but not in the Ang II infusion model of hypertension.


Assuntos
Pressão Sanguínea/fisiologia , Gânglios Espinais/metabolismo , Coração/inervação , Hipertensão/metabolismo , Canais de Cátion TRPV/agonistas , Angiotensina II , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Diterpenos/farmacologia , Gânglios Espinais/efeitos dos fármacos , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hipertensão/induzido quimicamente , Masculino , Neurotoxinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Reflexo/efeitos dos fármacos , Reflexo/fisiologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo
15.
Life Sci ; 233: 116745, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31404524

RESUMO

Hypertension is one of the major risk factors for cardiovascular disease worldwide and is striking more young people, which is characterized by impaired vascular endothelial function. To find the functional lncRNAs associated with hypertension, high throughput lncRNA microarray were used to analyze expression profile of the lncRNAs in the aortic vascular endothelial cells (VECs) of spontaneously hypertensive rats (SHRs). The tail vein injection of siRNA was used to study the influence of lncRNA AK094457 inhibition on endothelial function in vivo. In vitro, endothelial function was studied in endothelial cells transfected with lncRNA AK094457-overexpressed vectors and siRNAs. pPPARγ and iNOS protein levels were detected with Western blot. Elisa assay was used to analyze the secretion of AngII, ET-1, ROS and LDH level. The nitrite/nitrate (NO2-/NO3-) concentration was measured using a colorimetric assay. LncRNA AK094457 was a most upregulated lncRNA in SHRs. It is showed that downregulation of AK094457 significantly reduced rat arterial pressure, increased activation of endothelial PPARγ, and suppressed serum contents of AngII and NO in vivo. Furthermore, results from gain-and-loss of function in primary aortic endothelial cells indicated that AK094457 negatively regulated activation of PPARγ and promoted AngII-mediated endothelial dysfunction, manifested by decreased capacities of cell proliferation and migration, and increased levels of ROS production and LDH release. In conclusion, lncRNA AK094457 is identified as a key regulator in blood pressure and endothelial function, which can increase AngII-induced hypertension and endothelial dysfunction via suppression of PPARγ.


Assuntos
Angiotensina II/toxicidade , Endotélio Vascular/patologia , Hipertensão/patologia , Músculo Liso Vascular/patologia , PPAR gama/antagonistas & inibidores , RNA Longo não Codificante/genética , Vasoconstritores/toxicidade , Animais , Proliferação de Células , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Hipertensão/induzido quimicamente , Hipertensão/genética , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Ratos , Ratos Endogâmicos SHR , Transdução de Sinais , Remodelação Vascular
16.
Adv Exp Med Biol ; 1155: 173-182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468396

RESUMO

Taurine plays an important role in the modulation of cardiovascular function by acting not only within the brain but also within peripheral tissues. We found that IV injection of taurine to male rats caused hypotension and tachycardia. A single injection of taurine significantly lowered the systolic, diastolic and mean arterial pressure blood pressure in freely moving long Evans control rats. Previousely, we found that the endothelial cells express high levels of taurine transporters and GABAA receptors and showed that taurine activates GABAA receptors. Thus we suggest that the functional implication of GABAA receptors activation is the relaxation of the arterial muscularis, vasodilation and a decrease in blood pressure. Interestingly however, the effects of acute taurine injection were very different that chronic supplementation of taurine. When rats were supplemented taurine (0.05%, 4 weeks) in their drinking water, taurine has significant hypertensive properties. The increase in blood pressure was observed however only in females, males supplemented with taurine did not show an increase in systolic, diastolic or mean arterial pressure. In both genders however, taurine supplementation caused a significant tachycardia. Thus, we suggest that acute administration of taurine may be beneficial to lowering blood pressure. However, our data indicate that supplementation of taurine to females caused a significant increase in blood pressure. It remains to be seen the effect of taurine supplementation on hypertensive rats.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Fatores Sexuais , Taurina/farmacologia , Animais , Feminino , Hemodinâmica , Masculino , Ratos , Taquicardia/induzido quimicamente
17.
Muscle Nerve ; 60(5): 528-537, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31443119

RESUMO

INTRODUCTION: Although intravenous immune globulin (IVIg) is used to treat patients in the outpatient setting, there is limited documentation addressing the safety of this practice. METHODS: Retrospective analysis of 438 patients with neuromuscular diseases receiving IVIg in an outpatient setting. RESULTS: Adverse events (AE) overall occurred in 16.9% of patients. Headache was the most common AE, noted in 11.6% of patients. Serious AEs occurred in 0.91% of patients; aseptic meningitis was the only one noted. Multivariate analyses identified the following risk factors for AEs: first-lifetime course of IVIg, higher dose per course of IVIg, diagnosis of myasthenia gravis, women, and younger age. DISCUSSION: Intravenous immune globulin is generally safe to administer in an outpatient setting. Women, myasthenia gravis patients, and those receiving their first course or a higher total dose of IVIg are at an increased risk of experiencing an AE.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Doenças Neuromusculares/terapia , Adulto , Fatores Etários , Idoso , Assistência Ambulatorial , Exantema/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Humanos , Hipertensão/induzido quimicamente , Infusões Intravenosas , Masculino , Meningite Asséptica/induzido quimicamente , Pessoa de Meia-Idade , Análise Multivariada , Miastenia Gravis/terapia , Miosite/terapia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
18.
Future Oncol ; 15(24s): 27-33, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393171

RESUMO

Lenvatinib significantly prolonged progression-free survival versus placebo in patients with radio-iodine refractory differentiated thyroid carcinoma. However, the primary adverse effects of any grade that occurred in >40% of patients in the lenvatinib group of the Phase III SELECT trial was hypertension (67.8%). Therefore, this drug should be used with caution in patients with cardiological morbidity. Here, we describe the case of a 73-year-old man with hypertension, obesity and chronic atrial fibrillation, who received lenvatinib for 6 months in the absence of cardiological symptoms.


Assuntos
Anormalidades Cardiovasculares/tratamento farmacológico , Hipertensão/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Câncer Papilífero da Tireoide/tratamento farmacológico , Idoso , Anormalidades Cardiovasculares/complicações , Anormalidades Cardiovasculares/diagnóstico por imagem , Anormalidades Cardiovasculares/patologia , Terapia Combinada , Humanos , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico por imagem , Hipertensão/patologia , Masculino , Compostos de Fenilureia/efeitos adversos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Quinolinas/efeitos adversos , Ablação por Radiofrequência/métodos , Câncer Papilífero da Tireoide/complicações , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia
19.
Hypertension ; 74(4): 936-946, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378107

RESUMO

Endothelial cells regulate vascular tone by producing both relaxing and contracting factors to control the local blood flow. Hypertension is a common side effect of mTORC1 (mammalian target of rapamycin complex 1) inhibitors. However, the role of endothelial mTORC1 in hypertension remains elusive. The present study aimed to determine the role of endothelial mTORC1 in Ang II (angiotensin II)-induced hypertension and the underlying mechanism. Endothelial mTORC1 activity was increased by Ang II both in vitro and in vivo. Blood pressure was higher in Tie-2-Cre-mediated regulatory associated protein of mTOR (mammalian target of rapamycin; Raptor) heterozygous-deficient (Tie2Cre-RaptorKD) mice than control mice both before and after Ang II infusion. Acetylcholine-evoked endothelium-dependent relaxation of mesenteric arteries was impaired in Tie2Cre-RaptorKD mice. Treatment with indomethacin or a specific COX (cyclooxygenase)-2 inhibitor, NS-398, but not L-NG-nitroarginine methyl ester reduced endothelium-dependent relaxation in Raptorflox/- mice to a similar extent as in Tie2Cre-RaptorKD mice. Metabolomic profiling revealed that the plasma content of prostaglandin E2 was reduced in Tie2Cre-RaptorKD mice with or without Ang II infusion. In endothelial cells, reduction of the protein level of YAP (yes-associated protein) with siRNA-mediated RPTOR deficiency was autophagy dependent and transcriptionally regulated the expression of COX-2 and mPGES-1 (microsomal prostaglandin E synthase-1). Hence, overexpression of YAP in endothelial cells enhanced the mRNA and protein levels of COX-2 and mPGES-1 and reversed the endothelial dysfunction and hypertension in Tie2Cre-RaptorKD mice. The present results demonstrate that suppression of mTORC1 activity in endothelial cells reduces prostaglandin E2 production and causes hypertension by reducing YAP-mediated COX-2/mPGES-1 expression.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Pressão Sanguínea/fisiologia , Endotélio Vascular/metabolismo , Hipertensão/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fosfoproteínas/metabolismo , Transdução de Sinais/fisiologia , Angiotensina II , Animais , Pressão Sanguínea/efeitos dos fármacos , Proteínas de Ciclo Celular , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Hipertensão/induzido quimicamente , Indometacina/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Camundongos , Prostaglandina-E Sintases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
20.
Arch Environ Contam Toxicol ; 77(4): 490-500, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31363802

RESUMO

Metals from the natural environment have potential hypertension effects. However, relevant studies on this topic are few. A total of 1358 adults aged 18-74 years from Chizhou, Maanshan, and Tongling of Anhui Province participated in the baseline study from 2014 to 2015. The follow-up study was performed from 2016 to 2017. Inductively coupled plasma optical emission spectrometry (7000 DV) was used to measure urinary Cr, Mn, Fe, Cu, and Zn of residents. Urinary concentrations of Cd determined via TAS-900 atomic absorption spectrophotometry at 228.8 nm wavelength. A total of 275 hypertension cases were identified. After adjusting for sociodemographic factors and risk factors for hypertension, four metals (Cd, Cr, Cu, and Mn) were significantly associated with hypertension in the single-metal model. Upon including all metals in the same model, the hazard ratios of the highest quartiles Cd and Cu compared with the reference group were 1.42 (95% confidence interval [CI] 1.09-2.02) and 1.56 (95% CI 1.16-2.09) for cases of hypertension. Our findings suggested that high levels of Cd and Cu might increase the incidence of hypertension. Further studies involving larger population should be conducted to confirm these findings.


Assuntos
Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Metais Pesados/urina , Adulto , Idoso , China/epidemiologia , Exposição Ambiental/efeitos adversos , Feminino , Seguimentos , Humanos , Hipertensão/urina , Incidência , Masculino , Metais Pesados/análise , Metais Pesados/toxicidade , Pessoa de Meia-Idade , Fatores de Risco , Poluentes do Solo/análise , Espectrofotometria Atômica
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