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1.
Proc Natl Acad Sci U S A ; 117(29): 17369-17380, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32641503

RESUMO

Voltage-gated L-type Ca2+ channel (Cav1.2) blockers (LCCBs) are major drugs for treating hypertension, the preeminent risk factor for heart failure. Vascular smooth muscle cell (VSMC) remodeling is a pathological hallmark of chronic hypertension. VSMC remodeling is characterized by molecular rewiring of the cellular Ca2+ signaling machinery, including down-regulation of Cav1.2 channels and up-regulation of the endoplasmic reticulum (ER) stromal-interacting molecule (STIM) Ca2+ sensor proteins and the plasma membrane ORAI Ca2+ channels. STIM/ORAI proteins mediate store-operated Ca2+ entry (SOCE) and drive fibro-proliferative gene programs during cardiovascular remodeling. SOCE is activated by agonists that induce depletion of ER Ca2+, causing STIM to activate ORAI. Here, we show that the three major classes of LCCBs activate STIM/ORAI-mediated Ca2+ entry in VSMCs. LCCBs act on the STIM N terminus to cause STIM relocalization to junctions and subsequent ORAI activation in a Cav1.2-independent and store depletion-independent manner. LCCB-induced promotion of VSMC remodeling requires STIM1, which is up-regulated in VSMCs from hypertensive rats. Epidemiology showed that LCCBs are more associated with heart failure than other antihypertensive drugs in patients. Our findings unravel a mechanism of LCCBs action on Ca2+ signaling and demonstrate that LCCBs promote vascular remodeling through STIM-mediated activation of ORAI. Our data indicate caution against the use of LCCBs in elderly patients or patients with advanced hypertension and/or onset of cardiovascular remodeling, where levels of STIM and ORAI are elevated.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Hipertensão/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Molécula 2 de Interação Estromal/metabolismo , Moléculas de Interação Estromal/metabolismo , Remodelação Vascular/fisiologia , Animais , Anti-Hipertensivos/farmacologia , Cálcio/metabolismo , Canais de Cálcio Tipo L/efeitos dos fármacos , Membrana Celular/metabolismo , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Retículo Endoplasmático/metabolismo , Técnicas de Inativação de Genes , Células HEK293 , Insuficiência Cardíaca , Humanos , Proteínas de Membrana/genética , Miócitos de Músculo Liso , Proteínas de Neoplasias , Proteína ORAI1/genética , Ratos , Molécula 1 de Interação Estromal/genética , Molécula 2 de Interação Estromal/genética
2.
Turk Kardiyol Dern Ars ; 48(4): 410-424, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-595169

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Infecções por Coronavirus/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/terapia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiarrítmicos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/toxicidade , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/toxicidade , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/toxicidade , Interações Medicamentosas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Pandemias , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Agregação de Plaquetas/toxicidade , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Vasodilatadores/toxicidade
3.
PLoS One ; 15(6): e0234269, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32598349

RESUMO

The aim of this study was to investigate pre- and post-diagnostic use of antihypertensive drugs on prostate cancer (PCa)-specific survival and the initiation of androgen deprivation therapy (ADT). The cohort investigated 8,253 PCa patients with 837 PCa-specific deaths during the median follow-up of 7.6 years after diagnosis. Information on drug use, cancer incidence, clinical features of PCa, and causes of death was collected from Finnish registries. Hazard ratios with 95% confidence intervals were calculated using Cox regression with antihypertensive drug use as a time-dependent variable. Separate analyses were performed on PCa survival related to pre- and post-diagnostic use of drugs and on the initiation of ADT. Antihypertensive drug use overall was associated with an increased risk of PCa-specific death (Pre-PCa: 1.21 (1.04-1.4), Post-PCa: 1.2 (1.02-1.41)). With respect to the separate drug groups, angiotensin II type 1 receptor (ATr) blockers, were associated with improved survival (Post-PCa: 0.81 (0.67-0.99)) and diuretics with an increased risk (Post-PCa: 1.25 (1.05-1.49)). The risk of ADT initiation was slightly higher among antihypertensive drug users as compared to non-users. In conclusion, this study supports anti-cancer effect of ATr blockers on PCa prognosis and this should be investigated further in controlled clinical trials.


Assuntos
Anti-Hipertensivos/farmacologia , Neoplasias da Próstata/mortalidade , Idoso , Estudos de Coortes , Progressão da Doença , Finlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Risco
4.
Turk Kardiyol Dern Ars ; 48(4): 410-424, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32519978

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Infecções por Coronavirus/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/terapia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiarrítmicos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/toxicidade , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/toxicidade , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/toxicidade , Interações Medicamentosas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Pandemias , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Agregação de Plaquetas/toxicidade , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Vasodilatadores/toxicidade
5.
Chem Biol Interact ; 326: 109145, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32485150

RESUMO

The renin-angiotensin-aldosterone system (RAAS) is a hormonal system that has a critical role in maintaining the normotensive state and electrolyte balance of the organism. The RAAS also has an important influence in the development of various pathophysiological conditions especially those concerning the renal system, cardiovascular system and hypertension. One of the consequences of the RAAS system is an increase in the generation of the reactive oxygen species (ROS) that causes an increase in oxidative stress, which may play a role in the development or exacerbation of such pathological conditions. Blocking this system at multiple points has been advantageous in the clinical management of these disorders. The key blockers that had gained predominant clinical use for such manifestations were angiotensin receptor blockers and angiotensin-converting enzyme (ACE) inhibitors. However, their prolonged use caused a compensatory increase in renin and angiotensin I levels. The blocking of the system at the initial stages by blocking renin was of advantage to overcome such compensation. Such a renin blocker that gained widespread use was aliskiren. It is the first oral renin inhibitor that was approved for use in 2007. Although the opinions are varied about the use and future of renin inhibitors as antihypertensive agents, aliskiren has been well documented to have antioxidant effects. Aliskiren functions as an antioxidant by lowering the increase in ROS that are produced by the RAAS system at doses independent of decreasing the blood pressure. In the present review we discuss the antioxidant properties of aliskiren independent of its blood pressure lowering property.


Assuntos
Amidas/farmacologia , Amidas/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fumaratos/farmacologia , Fumaratos/uso terapêutico , Hipertensão/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/metabolismo , Espécies Reativas de Oxigênio/metabolismo
6.
Hipertens Riesgo Vasc ; 37(4): 169-175, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32527699

RESUMO

The first case of COVID-19 was reported on 31 December 2019 in Wuhan, China. Ever since there has been unprecedented and growing interest in learning about all aspects of this new disease. Debate has been generated as to the association between antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors and SARS-CoV-2 infection. While many questions as yet remain unanswered, the aim of this report is to inform health professionals about the current state of knowledge. Because this is an ever-evolving topic, the recommendation is that it be updated as new evidence becomes available. Below, we provide a review of pre-clinical and clinical studies that link coronavirus to the RAAS.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Proteína ADAM17/fisiologia , Angiotensina II/fisiologia , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Pulmão/fisiopatologia , Modelos Biológicos , Pandemias/prevenção & controle , Peptidil Dipeptidase A/efeitos dos fármacos , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Receptores Virais/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Serina Endopeptidases/fisiologia , Vacinas Virais , Internalização do Vírus/efeitos dos fármacos
7.
Hipertens Riesgo Vasc ; 37(4): 176-180, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32591283

RESUMO

The association between hypertension, diabetes, cardio and cerebrovascular disease and severe and fatal COVID-19, described in different countries, is remarkable. Myocardial damage and myocardial dysfunction are postulated as a possible causal nexus. Frequent findings of elevated troponin levels and electrocardiographic anomalies support this concept. On the other hand, hypotheses in favour and against a deleterious effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, a usual treatment for cardiovascular disease, have been raised. There is currently no solid evidence and thus properly designed studies on this subject are urgently needed. In this context, patients with cardiovascular disease should especially avoid being exposed to the virus, should not self-medicate and rapidly seek medical advice should they show symptoms of infection.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Fatores Etários , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Diagnóstico Precoce , Coração/fisiopatologia , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Pessoa de Meia-Idade , Miocardite/etiologia , Miocardite/fisiopatologia , Peptidil Dipeptidase A/efeitos dos fármacos , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Receptores Virais/efeitos dos fármacos , Receptores Virais/fisiologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Fatores de Risco , Automedicação
8.
Expert Opin Pharmacother ; 21(10): 1167-1178, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32543325

RESUMO

INTRODUCTION: Office blood pressure measurements (OBPM), still used today for diagnosis and management of hypertension, fail to reveal clinically important features of the mostly predictable blood pressure (BP) 24 h pattern, and lead to >45% of individuals being misclassified. Current hypertension guidelines do not provide recommendation on when-to-treat, despite multiple prospective clinical trials documenting improved normalization of 24 h BP pattern and significant reduction in cardiovascular disease (CVD) events when hypertension medications are ingested at bedtime rather than upon waking. AREAS COVERED: In this review, the authors discuss current evidence on the: (i) most relevant attributes of the 24 h BP pattern deterministic of CVD risk; (ii) asleep systolic BP (SBP) mean as the most significant therapeutic target for CVD risk reduction; (iii) ingestion-time differences in pharmacodynamics of BP-lowering medications as reported with high consistency in multiple clinical trials; and (iv) enhanced prevention of CVD events achieved by bedtime hypertension chronotherapy. EXPERT OPINION: Several prospective trials consistently document asleep SBP mean and sleep-time relative SBP decline (dipping) constitute highly significant CVD risk factors, independent of OBPM. Bedtime, compared to customary upon-waking, hypertension chronotherapy reduces risk of major CVD events. Collectively, these findings call for new definition of true hypertension and, accordingly, its proper diagnosis and management.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/farmacologia , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Estudos Prospectivos
11.
PLoS One ; 15(5): e0233788, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470081

RESUMO

In pre-hypertension, moderate control of blood pressure (BP) can be obtained by a nutritional approach. The effects of a diet enriched with defatted larvae of the mealworm Tenebrio molitor (Coleoptera: Tenebrionidae) (TM) endowed with ACE inhibitory activity was studied in both spontaneously hypertensive rats (SHR) and in the age-matched normotensive Wistar Kyoto strain. These were fed for 4 weeks with standard laboratory rodent chow supplemented with or without TM or captopril. In SHR, the TM diet caused a significant reduction in BP, heart rate and coronary perfusion pressure, as well as an increase in red blood cell glutathione/glutathione disulphide ratio. Rat brain slices of SHR were more resistant to oxidative stress and contained lower levels of inflammatory cytokines, while vascular and liver enzyme-activities were not affected. These results suggest that TM can be considered a new functional food that can lower BP in vivo and thus control cardiovascular-associated risk factors such as hypertension.


Assuntos
Pressão Sanguínea , Suplementos Nutricionais , Frequência Cardíaca , Hipertensão/dietoterapia , Animais , Anti-Hipertensivos/farmacologia , Captopril/farmacologia , Hipertensão/tratamento farmacológico , Larva , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Tenebrio
14.
Vasc Med ; 25(4): 295-301, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32469270

RESUMO

Preeclampsia is a life-threatening multiorgan systemic disease with manifestations including gestational hypertension, oxidative stress, and vascular dysfunction. We aimed to evaluate the therapeutic effects of melatonin on an L-NAME (NLG-nitro-l-arginine methyl ester)-induced rat preeclampsia model. During gestation, L-NAME was added to drinking water at 50 mg/kg/day from gestation day (GD) 8. Rats received the combination of L-NAME with melatonin (10 mg/kg/day), or aspirin (1.5 mg/kg/day), and rats that received only L-NAME or no treatments were used as controls. Aspirin was mixed with rodent chow and melatonin was administered intraperitoneally. Blood pressure and urine protein content were monitored every 3 days. On GD19, blood samples were collected for biochemical analysis. Compared to untreated L-NAME rats, melatonin led to markedly lowered blood pressure and urine protein content, and recovery in the fetus alive ratio, fetal weight, and the fetal weight/placental weight ratio. Compared to untreated L-NAME rats, plasma antioxidant capacity and plasma malondialdehyde were increased and decreased by melatonin, respectively, in L-NAME rats. Melatonin treatment also reduced sFlt-1, increased PlGF, and decreased the sFlt-1/PlGF ratio. In the placenta, melatonin also reduced sFlt-1 levels and increased Nrf2, PlGF, and HO-1 levels. We have demonstrated in a rat model of preeclampsia that melatonin exerts significant protective effects through lowering blood pressure and reducing oxidative stress.


Assuntos
Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão Induzida pela Gravidez/prevenção & controle , Melatonina/farmacologia , NG-Nitroarginina Metil Éster , Estresse Oxidativo/efeitos dos fármacos , Placenta/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Heme Oxigenase (Desciclizante)/metabolismo , Hipertensão Induzida pela Gravidez/induzido quimicamente , Hipertensão Induzida pela Gravidez/metabolismo , Hipertensão Induzida pela Gravidez/fisiopatologia , Fator 2 Relacionado a NF-E2/metabolismo , Placenta/metabolismo , Placenta/fisiopatologia , Fator de Crescimento Placentário/metabolismo , Gravidez , Proteinúria/induzido quimicamente , Proteinúria/metabolismo , Proteinúria/fisiopatologia , Proteinúria/prevenção & controle , Ratos Sprague-Dawley , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
16.
Adv Exp Med Biol ; 1177: 149-268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32246447

RESUMO

Hypertension is still the number one global killer. No matter what causes are, lowering blood pressure can significantly reduce cardiovascular complications, cardiovascular death, and total death. Unfortunately, some hypertensive individuals simply do not know having hypertension. Some knew it but either not being treated or treated but blood pressure does not achieve goal. The reasons for inadequate control of blood pressure are many. One important reason is that we are not very familiar with antihypertensive agents and less attention has been paid to comorbidities, complications as well as the hypertension-modified target organ damage in patients with hypertension. The right antihypertensive drug was not given to the right hypertensive patients at right time. This reviewer studied comprehensively the literature, hopefully that the review will help improve antihypertensive drug selection and antihypertensive therapy.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Humanos
17.
PLoS One ; 15(4): e0231244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298274

RESUMO

BACKGROUND: Quantifying dose-dependent ultra-early edema and ultrastructural changes in the myocyte after drug delivery is important for the development of new mixed calcium channel blockers (CCBs). MATERIALS AND METHODS: Arterial cannulation was used to measure mean arterial pressure in real time; simultaneously, magnetic resonance imaging proton density mapping was used to quantify edema 5-55 min after the delivery of L-type CCBs, T- and L-type CCBs, and solvent to a spontaneously hypertensive rat model. Transmission electron microscopy was used to show ultrastructural changes in the myocyte. RESULTS: Analysis of variance showed significant differences among the three groups in mean arterial pressure reduction (F = 246.36, P = 5.75E-25), ultra-early level of edema (ULE) (F = 175.49, P = 5.62E-22), and dose-dependent level of edema (DLE) (F = 199.48, P = 4.28E-23). Compared with the solvent's mean arterial pressure reduction (2.65±6.56±1.64), ULE (1.16±0.09±0.02), and DLE (0.0010±0.0001±0.0000), post hoc tests showed that T- and L-type CCBs had better mean arterial pressure reduction (90.67±11.58±2.90, P = 1.06E-24 vs. 68.34±15.19±3.80, P = 1.76E-12), lower ULE (1.53±0.14±0.04, P = 4.74E-9 vs. 2.08±0.18±0.04, P = 2.68E-22), and lower DLE (0.0025±0.0004±0.0001, P = 1.14E-11 vs. 0.0047±0.0008±0.0002, P = 2.10E-11) than L- type CCBs. Transmission electron microscopy showed that T- and L-type CCBs caused fewer ultrastructural changes in the myocytes after drug delivery than L-type CCBs. CONCLUSION: T- and L-type CCBs produced less ultra-early and dose-dependent edema, fewer ultrastructural changes in the myocyte, and a greater antihypertensive effect. Proton density mapping combined with arterial cannulation and transmission electron microscopy allowed for quantification of ultra-early and dose-dependent edema, antihypertensive efficacy, and ultrastructural changes in the myocyte. This is important for the evaluation of induced vasodilatory edema.


Assuntos
Anti-Hipertensivos/farmacologia , Artérias/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Edema/diagnóstico , Hipertensão/tratamento farmacológico , Células Musculares/efeitos dos fármacos , Animais , Anti-Hipertensivos/administração & dosagem , Artérias/fisiopatologia , Bloqueadores dos Canais de Cálcio/administração & dosagem , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo T/metabolismo , Edema/induzido quimicamente , Ratos , Ratos Endogâmicos SHR
18.
Clin Hemorheol Microcirc ; 75(3): 279-289, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280080

RESUMO

OBJECTIVE: This study aims to investigate the effect of nimodipine combined with betahistine on the levels of CRP and other inflammatory cytokines, as well as vascular endothelial function in patients with hypertensive cerebral vasospasm. METHODS: A total of 80 patients with hypertensive cerebral vasospasm from March 2016 to September 2018 were enrolled and randomly equally divided into two groups. At 1 week before enrollment, the application of all antihypertensive drugs was stopped. Then amlodipine tablets were used in control group, based on which nimodipine tablets were applied in observation group. All the patients included were followed up for 1 month. The changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were measured and compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared, while the adverse reactions and the overall clinical treatment effect of the two groups were evaluated. RESULTS: The cerebral vasospasm indexes in observation group were significantly lower than those in control group at 3 d, 1 week and 1 month after treatment (p < 0.05). At 1 month after treatment, the levels of inflammatory cytokines such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in observation group were significantly reduced compared to those in control group (p < 0.05). As for vascular endothelial function-related indicators, the endothelin-1 (ET-1) level in observation group was markedly lower than that in control group, whereas the level of nitric oxide (NO) was statistically higher than that in control group (p < 0.05). The cerebral vasospasm index was statistically positively correlated with changes in hs-CRP, IL-6, TNF-α and ET-1 (p < 0.05), but negatively correlated with changes in NO (p < 0.05). Besides, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were significantly higher than those in control group (p < 0.05). The overall treatment effective rate in observation group was markedly higher than that in control group (p < 0.05), and there were no significant differences of adverse reactions between the two groups (p > 0.05). CONCLUSION: For the treatment of hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body's aseptic inflammatory responses, improve vascular endothelial function and increase the cerebral circulation blood flow, which offers a favorable strategy for clinical therapy.


Assuntos
Anti-Hipertensivos/uso terapêutico , beta-Histina/uso terapêutico , Proteína C-Reativa/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Nimodipina/uso terapêutico , Vasodilatadores/uso terapêutico , Vasoespasmo Intracraniano/tratamento farmacológico , Idoso , Anti-Hipertensivos/farmacologia , beta-Histina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nimodipina/administração & dosagem , Vasodilatadores/farmacologia
19.
Expert Opin Pharmacother ; 21(10): 1269-1282, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32228188

RESUMO

INTRODUCTION: Fixed-combination glaucoma medications have altered the paradigm of ocular hypertension and glaucoma treatment and are in widespread use today. A comprehensive review of fixed-combination medications will help educate and inform providers for optimal patient care. AREAS COVERED: In this review, the authors describe the composition, mechanism of action, efficacy, side effects, and safety profile of fixed-combination agents for the treatment of ocular hypertension and glaucoma as well as comparisons between the most frequently prescribed medications. EXPERT OPINION: Fixed-combination therapeutics provide an effective and efficient means of lowering intraocular pressure with comparable side effects and outcomes to constituent parts with lower patient exposure to preservatives and improvement in compliance.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Ocular/tratamento farmacológico , Soluções Oftálmicas/uso terapêutico , Anti-Hipertensivos/farmacologia , Humanos , Soluções Oftálmicas/farmacologia
20.
Expert Opin Pharmacother ; 21(10): 1219-1240, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32281890

RESUMO

INTRODUCTION: Hypertension is highly prevalent in patients with end-stage kidney disease on hemodialysis and is often not well controlled. Blood pressure (BP) levels before and after hemodialysis have a U-shaped relationship with cardiovascular and all-cause mortality. Although antihypertensive drugs are recommended for patients in whom BP cannot be controlled appropriately by non-pharmacological interventions, large-scale randomized controlled clinical trials are lacking. AREAS COVERED: The authors review the pharmacotherapy used in hypertensive patients on dialysis, primarily focusing on reports published since 2000. An electronic search of MEDLINE was conducted using relevant key search terms, including 'hypertension', 'pharmacotherapy', 'dialysis', 'kidney disease', and 'antihypertensive drug'. Systematic and narrative reviews and original investigations were retrieved in our research. EXPERT OPINION: When a drug is administered to patients on dialysis, the comorbidities and characteristics of each drug, including its dialyzability, should be considered. Pharmacological lowering of BP in hypertensive patients on hemodialysis is associated with improvements in mortality. ß-blockers should be considered first-line agents and calcium channel blockers as second-line therapy. Renin-angiotensin-aldosterone system inhibitors have not shown superiority to other antihypertensive drugs for patients on hemodialysis.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Diálise Renal/métodos , Anti-Hipertensivos/farmacologia , Humanos
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