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1.
Cell Physiol Biochem ; 53(4): 587-605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31535830

RESUMO

BACKGROUND/AIMS: To investigate the role of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in renal ischemia/reperfusion-induced (I/R) cardiac inflammatoryprofile. METHODS: Left kidney ischemia was induced in male C57BL/6 mice for 60 min, followed by reperfusion for 12 days, and treatment with or without atenolol, losartan, or enalapril. The expression of vimentin in kidney and atrial natriuretic factor (ANF) in the heart has been investigated by RT-PCR. In cardiac tissue, levels of ß1-adrenoreceptors, adenylyl cyclase, cyclic AMP-dependent protein kinase (PKA), noradrenaline, adrenaline (components of SNS), type 1 angiotensin II receptors (AT1R), angiotensinogen/Ang II and renin (components of RAS) have been measured by Western blotting and HPLC analysis. A panel of cytokines - tumour necrosis factor (TNF-α), interleukin IL-6, and interferon gamma (IFN-γ) - was selected as cardiac inflammatory markers. RESULTS: Renal vimentin mRNA levels increased by >10 times in I/R mice, indicative of kidney injury. ANF, a marker of cardiac lesion, increased after renal I/R, the values being restored to the level of Sham group after atenolol or enalapril treatment. The cardiac inflammatory profile was confirmed by the marked increase in the levels of mRNAs of TNF-α, IL-6, and IFN-γ. Atenolol and losartan reversed the upregulation of TNF-α expression, whereas enalapril restored IL-6 levels to Sham levels; both atenolol and enalapril normalized IFN-γ levels. I/R mice showed upregulation of ß1-adrenoreceptors, adenylyl cyclase, PKA and noradrenaline. Renal I/R increased cardiac levels of AT1R, which decreased after losartan or enalapril treatment. Renin expression also increased, with the upregulation returning to Sham levels after treatment with SNS and RAS blockers. Angiotensinogen/Ang II levels in heart were unaffected by renal I/R, but they were significantly decreased after treatment with losartan and enalapril, whereas increase in renin levels decreased. CONCLUSION: Renal I/R-induced cardiac inflammatory events provoked by the simultaneous upregulation of SNS and RAS in the heart, possibly underpin the mechanism involved in the development of cardiorenal syndrome.


Assuntos
Rim/metabolismo , Miocárdio/metabolismo , Sistema Renina-Angiotensina , Sistema Nervoso Simpático/metabolismo , Animais , Atenolol/farmacologia , Atenolol/uso terapêutico , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Catecolaminas/metabolismo , Enalapril/farmacologia , Enalapril/uso terapêutico , Interleucina-6/metabolismo , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Sistema Nervoso Simpático/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Vimentina/genética , Vimentina/metabolismo
2.
Biomed Pharmacother ; 118: 109394, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545259

RESUMO

The renin-angiotensin system (RAS) plays an important role in scar formation. We have previously shown that oral administration of ramipril and losartan could inhibit scarring. For easier application, here we developed a series of topical ramipril and losartan creams in different concentrations and formulations to explore the effect on scar formation in a C57BL/6 mouse scar model. The harvested scar tissues were analyzed with H&E staining, Masson staining and immunohistochemical staining. We found the group treated with 0.2% losartan urea cream (Prep. 1) or 0.1% ramipril cream (Prep. 2) had significantly smaller scars compared to the negative control, while the proliferation of fibroblasts was less active and the collagen fibers were more regular; both groups showed similar efficacy with the positive control (triamcinolone acetonide urea). We also found that drug transdermalness couldn't directly determine the efficacy. Our findings indicate that local application of angiotensin converting enzyme inhibitor drugs (ACEIs) and angiotensin receptor blocker drugs (ARBs) can reduce scarring by reducing the expression of collagen I, collagen III, phosphorylated small mothers against decapentaplegic 3 (p-Smad3) and transforming growth factor-ß 1 (TGF-ß1). This may provide new insight on scar treatment in clinic.


Assuntos
Cicatriz/tratamento farmacológico , Losartan/administração & dosagem , Losartan/uso terapêutico , Ramipril/administração & dosagem , Ramipril/uso terapêutico , Creme para a Pele/uso terapêutico , Administração Tópica , Animais , Cicatriz/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Losartan/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Proteína Smad3/metabolismo , Suínos , Fator de Crescimento Transformador beta1/metabolismo
3.
Med Arch ; 73(3): 157-162, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31391706

RESUMO

Introduction: Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardiovascular diseases (CVD). Aim: The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor. Methods: This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1st and 2nd follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR). Results: SBP, DPB, PP, and PWV significantly decreased from baseline to 2nd follow-up in all treatment groups. The mean reductions in SBP were from -11.7 (95%CI; 9.3- 14.1) to -23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from -5.5 (95%CI; 3.9- 7.1) to -13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from -3.3% to -8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2nd follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027). Conclusion: These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Idoso , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Artérias , Diástole/efeitos dos fármacos , Combinação de Medicamentos , Hipertensão Essencial/tratamento farmacológico , Feminino , Humanos , Hidroclorotiazida/farmacologia , Hidroclorotiazida/uso terapêutico , Lisinopril/farmacologia , Lisinopril/uso terapêutico , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso , Sístole/efeitos dos fármacos , Valsartana/farmacologia , Valsartana/uso terapêutico
4.
Blood Purif ; 48(3): 233-242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31387098

RESUMO

AIMS AND OBJECTIVE: To estimate the effect of losartan 50 mg on survival of post-dialysis euvolemic hypertensive patients. METHODOLOGY: A single center, prospective, single-blind randomized trial was conducted to estimate the survival of post-dialysis euvolemic hypertensive patients when treated with lorsartan 50 mg every other day. Post-dialysis euvolemic assessment was done by a body composition monitor. Covariate Adaptive Randomization was used for allocation of participants to the standard or intervention arm, and the follow-up duration was twelve months. The primary end point was achieving targeted blood pressure (BP) of <140/90 mm Hg and maintaining for 4 weeks, whereas secondary end point was all cause of mortality. Pre-, intra-, and post-dialysis session BP measurements were recorded, and survival trends were analyzed using Kaplan-Meier analysis. RESULTS: Of the total 229 patients, 96 (41.9%) were identified as post-dialysis euvolemic hypertensive. Final samples of 88 (40.1%) patients were randomized into standard (n = 44) and intervention arms (n = 44), and 36 (81.8%) patients in each arm completed a follow-up of 12 months. A total of eight patients passed away during the 12-month follow-up period (6 deaths among standard arm and 2 in intervention arm). However, the probability of survival between both arms was not significant (p = 0.13). Cox regression analysis revealed that chances of survival were higher among the patients in the intervention (OR 3.17) arm than the standard arm (OR 0.31); however, the survival was found not statistically significant. CONCLUSION: There was no statistical significant difference in 1 year survival of post-dialysis euvolemic hypertensive patients when treated with losartan 50 mg.


Assuntos
Hipertensão/tratamento farmacológico , Losartan/administração & dosagem , Adulto , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Feminino , Seguimentos , Humanos , Hipertensão/mortalidade , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Diálise Renal , Análise de Sobrevida , Falha de Tratamento
5.
Life Sci ; 234: 116775, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31425697

RESUMO

AIMS: The activation of the angiotensin (Ang) II after acute kidney injury (AKI) triggers oxidative stress and inflammatory cascade which involved not only the kidneys but also the brain. Ang II through the Ang II type 1 receptor (AT1R) may have deleterious effects on hippocampal synaptic transmission and cognitive functions under uremic encephalopathy. The present study was conducted to examine the effects of AT1R antagonist on AKI-induced cognitive and synaptic plasticity impairment. MAIN METHODS: Here, we investigated the effect of AKI and possible pathophysiological roles of AT1R with the selective AT1R antagonist losartan (10 mg/kg/day for consecutive 9 days) on cognitive performance using passive avoidance and Morris water maze tests. In order to understand the synaptic transmission, in vivo short and long-term plasticity were evaluated at the Schaffer collateral-CA1 synapse. Biochemical analysis was also performed to detect possible hippocampal nitric oxide and oxidative stress mechanisms. KEY FINDINGS: Our data provide evidence of hippocampal complication following AKI with increased level of nitrite (P < 0.01 vs. sham) as well as oxidative stress (P < 0.01 vs. sham) that may be responsible for behavioral dysfunction under uremia (spatial memory, P < 0.001; passive avoidance P < 0.01 vs. sham). Losartan treatment effectively protects against cognitive (spatial memory, P < 0.01; passive avoidance P < 0.05 vs. AKI-veh) and synaptic plasticity impairments induced by AKI possibly via modulation of oxidative stress in the hippocampus (P < 0.01 vs. AKI-veh). SIGNIFICANCE: The present study conclusively demonstrated a protective role of AT1R antagonist losartan in hippocampal complication and neurocognitive dysfunction after AKI via modulating oxidative stress.


Assuntos
Lesão Renal Aguda/complicações , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Hipocampo/efeitos dos fármacos , Losartan/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/fisiopatologia , Animais , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Memória/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo
6.
Int Urol Nephrol ; 51(11): 2073-2081, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401712

RESUMO

Obstructive nephropathy is a common cause for chronic kidney disease. Surgery, which is adopted to promptly relieve the obstruction, is the most important method to save damaged kidneys. However, earlier studies have shown that renal function will continue to deteriorate until the terminal stage after the obstruction' relief. The aim of this study is to explore the renal fibrosis and investigate the effect of losartan on renal fibrosis after the obstruction' relief using an improved mouse model of relief for unilateral ureteral obstruction (RUUO). Experiments carried out using C57BL/6 mice (n = 30) were randomly divided into RUUO + Losartan group, RUUO group and sham group. Using an improved mouse RUUO model, this study revealed that the mouse kidney for 3- or 7-day unilateral ureteral obstruction undergoing the RUUO surgery was still in a state of injury and fibrosis, while losartan could effectively ameliorate renal fibrosis by upregulating the expression of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) in kidney after the surgery of RUUO.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Rim/patologia , Losartan/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/fisiologia , Regulação para Cima/efeitos dos fármacos , Animais , Fibrose/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Fatores de Tempo , Resultado do Tratamento , Obstrução Ureteral/complicações , Obstrução Ureteral/cirurgia
7.
J Renin Angiotensin Aldosterone Syst ; 20(3): 1470320319862741, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31328615

RESUMO

INTRODUCTION: Telmisartan is an angiotensin-II receptor type-1 blocker and a partial agonist for peroxisome proliferator-activated receptor-γ. The aim of this study was to determine the potential effects of telmisartan on bone metabolism and turnover markers. METHODS: Forty-two patients with newly diagnosed stage I hypertension who were prescribed telmisartan 80 mg/day or losartan 100 mg/day were included. Serum levels of calcium, phosphorus, 25-hydroxy vitamin D, bone-specific alkaline phosphatase, osteocalcin, interleukin 6 and 24-hour urinary N-terminal telopeptide were measured at the beginning and after 12 weeks of treatment. RESULTS: When treatment arms were evaluated together, significantly increased 25-hydroxy vitamin D levels (p=0.01), and decreased parathormone (PTH) (p<0.001), bone-specific alkaline phosphatase (p=0.01), osteocalcin (p=0.045), urinary N-terminal telopeptide (p<0.001) and interleukin 6 levels (p=0.006) were observed. After eliminating the 25-hydroxy vitamin D effect, significant changes were not observed at any of the parameters. None of the levels of parameters were different between groups. CONCLUSIONS: Neither telmisartan, despite its partial peroxisome proliferator-activated receptor-γ agonistic effect, nor losartan treatment had significant effects on bone turnover markers in newly diagnosed stage I hypertensive patients.


Assuntos
Biomarcadores/sangue , Remodelação Óssea , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Losartan/uso terapêutico , Telmisartan/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Losartan/farmacologia , Masculino , Pessoa de Meia-Idade , Telmisartan/farmacologia
8.
J Am Soc Nephrol ; 30(6): 1049-1059, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31152118

RESUMO

BACKGROUND: In type 1 diabetes, changes in the GFR and urine albumin-to-creatinine ratio (ACR) are related to changes in kidney structure that reflect disease progression. However, such changes have not been studied in type 2 diabetes. METHODS: Participants were American Indians with type 2 diabetes enrolled in a clinical trial of losartan versus placebo. We followed a subset who underwent kidney biopsy at the end of the 6-year trial, with annual measurements of GFR (by urinary clearance of iothalamate) and ACR. Participants had a second kidney biopsy after a mean follow-up of 9.3 years. We used quantitative morphometric analyses to evaluate both biopsy specimens. RESULTS: Baseline measures for 48 participants (12 men and 36 women, mean age 45.6 years) who completed the study included diabetes duration (14.6 years), GFR (156 ml/min), and ACR (15 mg/g). During follow-up, glomerular basement membrane (GBM) width, mesangial fractional volume, and ACR increased, and surface density of peripheral GBM and GFR decreased. After adjustment for sex, age, ACR, and each morphometric variable at baseline, an increase in ACR during follow-up was significantly associated with increases in GBM width, mesangial fractional volume, and mean glomerular volume, and a decrease in surface density of peripheral GBM. Decline in GFR was not associated with changes in these morphometric variables after additionally adjusting for baseline GFR. CONCLUSIONS: In American Indians with type 2 diabetes and preserved GFR at baseline, increasing ACR reflects the progression of earlier structural glomerular lesions, whereas early GFR decline may not accurately reflect such lesions.


Assuntos
Albuminúria/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/patologia , Taxa de Filtração Glomerular/fisiologia , Losartan/uso terapêutico , Adulto , Análise de Variância , Biópsia por Agulha , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etnologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Índios Norte-Americanos/estatística & dados numéricos , Testes de Função Renal , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
9.
J Renin Angiotensin Aldosterone Syst ; 20(2): 1470320319851310, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31117912

RESUMO

INTRODUCTION: Bone marrow renin-angiotensin system(RAS) modulates acute myeloid leukaemia(AML).The aim of this study is to clarify the relationships between RAS and AML, and to show the effect of losartan and doxorubicin treatment in AML cell lines. METHODS: AML cell lines including CESS, HL-60, MO-1, P31/FUJ, GDM-1 and KASUMI-3 were used as models in this study. RESULTS: After treating the six AML cell lines with a combination of losartan and doxorubicin, they were divided into two groups based on their behaviour: one became more sensitive to drug treatment (Group A) and the other had no change observed in behaviour after drug treatment (Group B). In silico analyses showed that Group A is involved in cellular apoptosis, while Group B is involved in tumour angiogenesis further supporting the in vitro results. CONCLUSION: The combined treatment of the AML cell lines with losartan and doxorubicin resulted in an increase in sensitivity of some of the cell lines. Those leukaemic cells are modulated via the induction of apoptosis, whereas the other cells resistant to the drug treatment are closely related to tumour angiogenesis indicating that RAS-AT1R seems to be differently expressed in different leukaemic blast cells and tumour microenvironments. Pharmaco-biological actions of RAS inhibitors may be different in distinct leukaemic cells based on the pathological behaviour of AML genomic subtypes.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Losartan/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Losartan/farmacologia , Transdução de Sinais/efeitos dos fármacos
10.
Rev Med Chil ; 147(2): 173-180, 2019 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-31095165

RESUMO

BACKGROUND: To reduce the progression of chronic kidney disease (CKD) and cardiovascular risk, the guidelines recommend the blockade of the renin-angiotensin-aldosterone system (RAAS) in patients with proteinuria. AIM: To assess the frequency of enalapril or losartan use in diabetics or hypertensive patients with stage 3 CKD. MATERIAL AND METHODS: Review of clinical records of patients with CKD in an urban primary care clinic. RESULTS: We identified 408 subjects aged 40 to 98 years (66% women) with stage 3 CKD. Sixty six percent had only hypertension and 34% were diabetic with or without hypertension. Seventy four percent received RAAS blockers (52% used enalapril, 45% losartan and 2% both medications). RAAS blockers were used in 70% of hypertensive and 78% of diabetic patients. The prescription in hypertensive diabetics with microalbuminuria was lower than in those without microalbuminuria (72% vs 87%, p < 0.05), but the opposite occurred in pure hypertensive patients with and without microalbuminuria (88% vs 69%, p < 0.05). There were no significant differences in blood pressure levels, microalbuminuria or serum potassium levels between RAAS blocker users and non-users. No differences were observed either between enalapril and losartan users. CONCLUSIONS: The adherence to clinical guidelines is insufficient and users of the recommended drugs did not achieve the expected goals.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Enalapril/uso terapêutico , Losartan/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/urina , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/normas , Creatinina/sangue , Diabetes Mellitus/tratamento farmacológico , Progressão da Doença , Quimioterapia Combinada , Enalapril/administração & dosagem , Enalapril/normas , Feminino , Humanos , Hipertensão/tratamento farmacológico , Losartan/administração & dosagem , Losartan/normas , Masculino , Pessoa de Meia-Idade , Proteinúria/urina , Sistema Renina-Angiotensina , Cooperação e Adesão ao Tratamento/psicologia
11.
Arq Bras Cardiol ; 112(1): 87-90, 2019 01.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30673020

RESUMO

Blood pressure (BP)-lowering therapy improves left ventricular (LV) parameters of hypertensive target-organ damage in stage II hypertension, but whether there is a drug-class difference in echocardiographic parameters in stage I hypertension patients is less often studied. In the PREVER treatment study, where individuals with stage I hypertension were randomized for treatment with diuretics (chlorthalidone/amiloride) or losartan, 110 participants accepted to participate in a sub-study, where two-dimensional echocardiograms were performed at baseline and after 18 months of antihypertensive treatment. As in the general study, systolic BP reduction was similar with diuretics or with losartan. Echocardiographic parameters showed small but significant changes in both treatment groups, with a favorable LV remodeling with antihypertensive treatment for 18 months when target blood pressure was achieved either with chlorthalidone/amiloride or with losartan as the initial treatment strategy. In conclusion, even in stage I hypertension, blood pressure reduction is associated with improvement in echocardiographic parameters, either with diuretics or losartan as first-drug regimens.


Assuntos
Amilorida/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Diuréticos/uso terapêutico , Hipertensão/tratamento farmacológico , Losartan/uso terapêutico , Adulto , Idoso , Amilorida/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Diuréticos/farmacologia , Método Duplo-Cego , Ecocardiografia , Feminino , Seguimentos , Humanos , Hipertensão/diagnóstico por imagem , Losartan/farmacologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Remodelação Ventricular/efeitos dos fármacos
12.
Clin Exp Hypertens ; 41(5): 444-451, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30648895

RESUMO

Ficus deltoidea is used in Malay traditional medicine for the treatment of a number of disorders, including hypertension. There is, however, no scientific evidence on its anti-hypertensive effects. This study, therefore, investigated the effects of a standardized ethanolic-water extract of Ficus deltoidea Angustifolia (FD-A) on blood pressure (BP) in spontaneously hypertensive rats (SHR). Male SHR with systolic BP of >150 were divided into 4 groups (n = 8) and given either FD-A (800 or 1000 mg kg-1 day-1) or losartan (10 mg kg-1 day-1) or 0.5 ml of distilled water (control) daily for 28 days. BP, body weight, food and water intake, serum and urinary electrolytes, endothelin-1 (ET-1), total antioxidant capacity (TAC) and components of the renin-angiotensin-aldosterone system were measured. Data were analyzed using ANOVA with statistical significance set at p < 0.05. Following treatment, BP, heart rate, and heart weight in FD-A and losartan-treated rats were significantly lower than those in the controls. Serum TAC and urinary calcium excretion were significantly higher, whereas serum ET-1 concentration was significantly lower in FD-A treated rats when compared to those in controls. No significant differences were found in the components of the renin-angiotensin-aldosterone system between controls and FD-A treated rats. In conclusion, FD-A when given daily at doses of either 800 or 1000 mg kg-1 day-1 body weight reduces BP in SHR. This effect does not seem to involve the renin-angiotensin-aldosterone-system but might involve some other mechanisms. Abbreviations: FD-A: Ficus deltoidea Angustifolia; ACE: Angiotensin-converting enzyme; SHR: Spontaneously hypertensive rats; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; AUC: Area under curve; RAAS: Renin Angiotensin Aldosterone System.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Ficus , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Extratos Vegetais/uso terapêutico , Animais , Anti-Hipertensivos/uso terapêutico , Antioxidantes/metabolismo , Cálcio/urina , Endotelina-1/sangue , Etanol , Frequência Cardíaca/efeitos dos fármacos , Losartan/uso terapêutico , Masculino , Miocárdio/patologia , Tamanho do Órgão/efeitos dos fármacos , Fitoterapia , Ratos , Ratos Endogâmicos SHR , Sistema Renina-Angiotensina/efeitos dos fármacos , Água
13.
Arterioscler Thromb Vasc Biol ; 39(2): 126-136, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30651002

RESUMO

Thoracic aortic aneurysms that progress to acute aortic dissections are often fatal. Thoracic aneurysms have been managed with treatment with ß-adrenergic blocking agents (ß-blockers) and routine surveillance imaging, followed by surgical repair of the aneurysm when the risk of dissection exceeds the risk for repair. Thus, there is a window to initiate therapies to slow aortic enlargement and delay or ideally negate the need for surgical repair of the aneurysm to prevent a dissection. Mouse models of Marfan syndrome-a monogenic disorder predisposing to thoracic aortic disease-have been used extensively to identify such therapies. The initial finding that TGFß (transformation growth factor-ß) signaling was increased in the aortic media of a Marfan syndrome mouse model and that its inhibition via TGFß neutralization or At1r (Ang II [angiotensin II] type I receptor) antagonism prevented aneurysm development was generally viewed as a groundbreaking discovery that could be translated into the first cure of thoracic aortic disease. However, several large randomized trials of pediatric and adult patients with Marfan syndrome have subsequently yielded no evidence that At1r antagonism by losartan slows aortic enlargement more effectively than conventional treatment with ß-blockers. Subsequent studies in mouse models have begun to resolve the complex molecular pathophysiology underlying onset and progression of aortic disease and have emphasized the need to preserve TGFß signaling to prevent aneurysm formation. This review describes critical experiments that have influenced the evolution of our understanding of thoracic aortic disease, in addition to discussing old controversies and identifying new therapeutic opportunities.


Assuntos
Aneurisma Dissecante/terapia , Aneurisma da Aorta Torácica/terapia , Doença Aguda , Angiotensina II/fisiologia , Animais , Aneurisma da Aorta Torácica/etiologia , Humanos , Losartan/uso terapêutico , Camundongos , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/fisiologia
14.
Zhonghua Nei Ke Za Zhi ; 58(1): 74-77, 2019 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-30605956

RESUMO

A 22-year-old manpresented as a refractory nephrotic syndrome with edema and proteinuria for more than one year. Physical examination revealed facial steatadenomas and periungual fibromas. Images were characterized by hamartomatous lesions in multiple organs, including the central nervous system, heart, lungs, liver, and kidneys. Gene tests verified TSC2 mutation and confirmed the diagnosis of tuberous sclerosis complex. The APOL1 mutation was positive in this patient, which indicated the possibility of steroid-resistant focal segmental glomerulonephritis. Thus, he was treated with sirolimus. Renal angiomyolipoma was shrunk, but proteinuria was not relieved (24h unine protein>10 g) and eventually led into renal insufficiency. Nondialytic therapy was initiated consequently. Losartan 50 mg/d was used to control proteinuria under the close watch of serum creatinine. A recent phone call on October 2018 failed to reachthe patient. Therefore, the follow-up information was not updated.


Assuntos
Apolipoproteína L1/genética , Glomerulonefrite por IGA/tratamento farmacológico , Falência Renal Crônica/complicações , Losartan/uso terapêutico , Proteinúria/tratamento farmacológico , Sirolimo/uso terapêutico , Proteína 2 do Complexo Esclerose Tuberosa/genética , Esclerose Tuberosa/diagnóstico , Angiomiolipoma/tratamento farmacológico , Creatinina/sangue , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Mutação , Síndrome Nefrótica , Esclerose Tuberosa/tratamento farmacológico , Esclerose Tuberosa/genética , Adulto Jovem
15.
Rom J Intern Med ; 57(1): 7-13, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30375351

RESUMO

Cardiac sarcoidosis usually occurs in the context of systemic disease; however, isolated cardiac involvement can occur in up to 25% of cases and tends to be clinically silent. When symptoms are present, they are often nonspecific and occasionally fatal, representing a diagnostic challenge. A high index of clinical suspicion and the integration of appropriate imaging, laboratory, and pathologic findings is always required. Treatment aims to control the systemic inflammatory condition while preventing further cardiac damage. However, even with adequate diagnosis and treatment strategies, prognosis remains poor. We describe the case of a patient who presented with cardiac symptoms, whose initial examination was unrevealing. Diagnosis was made retrospectively based on later systemic manifestations that revealed characteristic sarcoidosis findings.


Assuntos
Cardiomiopatias/diagnóstico , Sarcoidose/diagnóstico , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/patologia , Fármacos Cardiovasculares/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Losartan/uso terapêutico , Metotrexato/uso terapêutico , Metoprolol/uso terapêutico , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia
16.
J Pediatr ; 204: 250-255.e1, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30270167

RESUMO

OBJECTIVE: To assess health-related quality of life (HRQOL) in a large multicenter cohort of children and young adults with Marfan syndrome participating in the Pediatric Heart Network Marfan Trial. STUDY DESIGN: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales were administered to 321 subjects with Marfan syndrome (5-25 years). PedsQL scores were compared with healthy population norms. The impact of treatment arm (atenolol vs losartan), severity of clinical features, and number of patient-reported symptoms on HRQOL was assessed by general linear models. RESULTS: Mean PedsQL scores in children (5-18 years) with Marfan syndrome were lower than healthy population norms for physical (P ≤ .003) and psychosocial (P < .001) domains; mean psychosocial scores for adults (19-25 years) were greater than healthy norms (P < .001). HRQOL across multiple domains correlated inversely with frequency of patient-reported symptoms (r = 0.30-0.38, P < .0001). Those <18 years of age with neurodevelopmental disorders (mainly learning disability, attention-deficit/hyperactivity disorder) had lower mean PedsQL scores (5.5-7.4 lower, P < .04). A multivariable model found age, sex, patient-reported symptoms, and neurodevelopmental disorder to be independent predictors of HRQOL. There were no differences in HRQOL scores by treatment arm, aortic root z score, number of skeletal features, or presence of ectopia lentis. CONCLUSIONS: Children and adolescents with Marfan syndrome were at high risk for impaired HRQOL. Patient-reported symptoms and neurodevelopmental disorder, but not treatment arm or severity of Marfan syndrome-related physical findings, were associated with lower HRQOL.


Assuntos
Anti-Hipertensivos/uso terapêutico , Atenolol/uso terapêutico , Losartan/uso terapêutico , Síndrome de Marfan/psicologia , Qualidade de Vida , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Adulto Jovem
18.
Chin Med J (Engl) ; 131(22): 2658-2665, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30425192

RESUMO

Background: Treatment with the dipeptidyl peptidase-4 inhibitors (DPP4i) and angiotensin receptor blockers (ARBs) in patients with type 2 diabetic nephropathy (DN) has not been well characterized. This study aimed to assess the renoprotection of this combined treatment in DN patients. Methods: A total of 159 type 2 DN patients from 2013 to 2015 were enrolled retrospectively from a prospective DN cohort at the National Clinical Research Center of Kidney Diseases, Jinling Hospital (China). Fifty-seven patients received DPP4i and ARB treatment, and 102 patients were treated with ARBs alone. All patients were followed up for at least 12 months. Statistical analyses were performed using Stata version 12.0. Results: There were no significant differences at baseline for age, sex, body mass index, duration of diabetes, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR) between the two groups. Antihypertensive and antidiabetic medication use was similar in each group except calcium channel antagonists (P = 0.032). No significant changes in FBG and HbA1c were observed in the two groups after treatment. The eGFR decreased slower in the DPP4i + ARB group than in the ARB group at 12 months (Δ12 months: -2.48 ± 13.86 vs. -6.81 ± 12.52 ml·min-1·1.73m-2, P = 0.044). In addition, proteinuria was decreased further in the DPP4i + ARB group than in the ARB group after 24 months of treatment (Δ24 months: -0.18 [-1.00, 0.17] vs. 0.32 [-0.35, 0.88], P = 0.031). There were 36 patients with an eGFR decrease of more than 30% over 24 months. After adjusting for FBG, HbA1c, and other risk factors, DPP4i + ARB treatment was still associated with a reduced incidence of an eGFR decrease of 20% or 30%. Conclusions: The combined treatment of DPP4i and ARBs is superior to ARBs alone, as evidenced by the greater proteinuria reduction and lower eGFR decline. In addition, the renoprotection of DPP4i combined with ARBs was independent of glycemic control.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Idoso , Feminino , Humanos , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
19.
Cochrane Database Syst Rev ; 10: CD009068, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30326162

RESUMO

BACKGROUND: The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further. OBJECTIVES: To assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM, using measures of change in cardiac function over six months. SEARCH METHODS: On 16 October 2017 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase, and on 12 December 2017, we searched two clinical trials registries. We also searched conference proceedings and bibliographies. SELECTION CRITERIA: We considered only randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials for inclusion. In the Discussion, we reviewed open studies, longitudinal observational studies and individual case reports but only discussed studies that adequately described the diagnosis, intervention, pretreatment, and post-treatment states and in which follow-up lasted for at least six months. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the titles and abstracts identified from the search and performed data extraction. All three authors assessed risk of bias independently, compared results, and decided which trials met the inclusion criteria. They assessed the certainty of evidence using GRADE criteria. MAIN RESULTS: We included five studies (N = 205) in the review; four studies included participants with DMD only, and one study included participants with DMD or BMD. All studied different interventions, and meta-analysis was not possible. We found no studies for XLDCM. None of the trials reported cardiac function as improved or stable cardiac versus deteriorated.The randomised first part of a two-part study of perindopril (N = 28) versus placebo (N = 27) in boys with DMD with normal heart function at baseline showed no difference in the number of participants with a left ventricular ejection fraction (LVEF%) of less than 45% after three years of therapy (n = 1 in each group; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.07 to 15.77). This result is uncertain because of study limitations, indirectness and imprecision. In a non-randomised follow-up study, after 10 years, more participants who had received placebo from the beginning had reduced LVEF% (less than 45%). Adverse event rates were similar between the placebo and treatment groups (low-certainty evidence).A study comparing treatment with lisinopril versus losartan in 23 boys newly diagnosed with Duchenne cardiomyopathy showed that after 12 months, both were equally effective in preserving or improving LVEF% (lisinopril 54.6% (standard deviation (SD) 5.19), losartan 55.2% (SD 7.19); mean difference (MD) -0.60% CI -6.67 to 5.47: N = 16). The certainty of evidence was very low because of very serious imprecision and study limitations (risk of bias). Two participants in the losartan group were withdrawn due to adverse events: one participant developed an allergic reaction, and a second exceeded the safety standard with a fall in ejection fraction greater than 10%. Authors reported no other adverse events related to the medication (N = 22; very low-certainty evidence).A study comparing idebenone versus placebo in 21 boys with DMD showed little or no difference in mean change in cardiac function between the two groups from baseline to 12 months; for fractional shortening the mean change was 1.4% (SD 4.1) in the idebenone group and 1.6% (SD 2.6) in the placebo group (MD -0.20%, 95% CI -3.07 to 2.67, N = 21), and for ejection fraction the mean change was -1.9% (SD 9.8) in the idebenone group and 0.4% (SD 5.5) in the placebo group (MD -2.30%, 95% CI -9.18 to 4.58, N = 21). The certainty of evidence was very low because of study limitations and very serious imprecision. Reported adverse events were similar between the treatment and placebo groups (low-certainty evidence).A multicentre controlled study added eplerenone or placebo to 42 patients with DMD with early cardiomyopathy but preserved left ventricular function already established on ACEI or ARB therapy. Results showed that eplerenone slowed the rate of decline of magnetic resonance (MR)-assessed left ventricular circumferential strain at 12 months (eplerenone group median 1.0%, interquartile range (IQR) 0.3 to -2.2; placebo group median 2.2%, IQR 1.3 to -3.1%; P = 0.020). The median decline in LVEF over the same period was also less in the eplerenone group (-1.8%, IQR -2.9 to 6.0) than in the placebo group (-3.7%, IQR -10.8 to 1.0; P = 0.032). We downgraded the certainty of evidence to very low for study limitations and serious imprecision. Serious adverse events were reported in two patients given placebo but none in the treatment group (very low-certainty evidence).A randomised placebo-controlled study of subcutaneous growth hormone in 16 participants with DMD or BMD showed an increase in left ventricular mass after three months' treatment but no significant improvement in cardiac function. The evidence was of very low certainty due to imprecision, indirectness, and study limitations. There were no clinically significant adverse events (very low-certainty evidence).Some studies were at risk of bias, and all were small. Therefore, although there is some evidence from non-randomised data to support the prophylactic use of perindopril for cardioprotection ahead of detectable cardiomyopathy, and for lisinopril or losartan plus eplerenone once cardiomyopathy is detectable, this must be considered of very low certainty. Findings from non-randomised studies, some of which have been long term, have led to the use of these drugs in daily clinical practice. AUTHORS' CONCLUSIONS: Based on the available evidence from RCTs, early treatment with ACE inhibitors or ARBs may be comparably beneficial for people with a dystrophinopathy; however, the certainty of evidence is very low. Very low-certainty evidence indicates that adding eplerenone might give additional benefit when early cardiomyopathy is detected. No clinically meaningful effect was seen for growth hormone or idebenone, although the certainty of the evidence is also very low.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Cardiomiopatia Dilatada/complicações , Distrofia Muscular de Duchenne/complicações , Adolescente , Adulto , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Cardiomiopatias/etiologia , Cardiomiopatias/prevenção & controle , Fármacos Cardiovasculares/uso terapêutico , Criança , Progressão da Doença , Eplerenona/efeitos adversos , Eplerenona/uso terapêutico , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Lisinopril/uso terapêutico , Losartan/uso terapêutico , Masculino , Ensaios Clínicos Controlados não Aleatórios como Assunto , Perindopril/uso terapêutico , Placebos/efeitos adversos , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume Sistólico/efeitos dos fármacos , Ubiquinona/efeitos adversos , Ubiquinona/análogos & derivados , Ubiquinona/uso terapêutico , Adulto Jovem
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