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[PMID]:27777360
[Au] Autor:Hwang AY; Dave C; Smith SM
[Ad] Endereço:From the Department of Pharmacotherapy and Translational Research (A.Y.H., S.M.S.) and Department of Pharmaceutical Outcomes and Policy (C.D.), College of Pharmacy, and Department of Community Health and Family Medicine, College of Medicine (A.Y.H., S.M.S.), University of Florida, Gainesville.
[Ti] Título:Trends in Antihypertensive Medication Use Among US Patients With Resistant Hypertension, 2008 to 2014.
[So] Source:Hypertension;68(6):1349-1354, 2016 12.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Little is known of US trends in antihypertensive drug use for patients with treatment-resistant hypertension (TRH). We analyzed antihypertensive use among patients with TRH (treated with ≥4 antihypertensive drugs concurrently) from July 2008 through December 2014 using Marketscan administrative data. We included adults aged 18 to 65 years, with ≥6 months of continuous enrollment, a hypertension diagnosis, and ≥1 episode of overlapping use of ≥4 antihypertensive drugs; patients with heart failure were excluded. We identified 411 652 unique TRH episodes from 261 652 patients with a mean age of 55.9 years. From 2008 to 2014, we observed an increased prevalence, among TRH episodes, of ß-blockers (+6.8% [79% to 85.8%]) and dihydropyridine calcium antagonists (+8.1% [69.1% to 77.2%]), and a decreased prevalence of angiotensin-converting enzyme inhibitors (-12.5% [60.4% to 47.9%]) and nondihydropyridine calcium antagonists (-5.0% [15% to 10%]). The prevalence of most other classes changed by <5% from 2008 to 2014. Thiazide diuretic use was largely unchanged from 2008 to 2014, with hydrochlorothiazide being by far the most prevalent thiazide diuretic; chlorthalidone use increased only modestly (+2.6% [3.8% to 6.4%]). Aldosterone antagonist use increased only modestly (+2.9% [7.3% to 10.2%]). Use of optimal regimens increased steadily (+13.8% [50.8% to 64.6%]) during the study period, whereas combined angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use declined (-11.4% [17.7% to 6.3%]). Our results highlight the persistent infrequent use of recommended therapies in TRH, including spironolactone and chlorthalidone, and suggest a need for better efforts to increase the use of such approaches in light of recent evidence demonstrating their efficacy.
[Mh] Termos MeSH primário: Anti-Hipertensivos/uso terapêutico
Clortalidona/uso terapêutico
Resistência a Medicamentos
Hipertensão/diagnóstico
Hipertensão/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico
Anti-Hipertensivos/farmacologia
Determinação da Pressão Arterial/métodos
Bloqueadores dos Canais de Cálcio/uso terapêutico
Estudos de Coortes
Quimioterapia Combinada
Uso de Medicamentos/tendências
Feminino
Seguimentos
Seres Humanos
Hidroclorotiazida/uso terapêutico
Masculino
Meia-Idade
Segurança do Paciente
Estudos Retrospectivos
Medição de Risco
Índice de Gravidade de Doença
Espironolactona/uso terapêutico
Resultado do Tratamento
Estados Unidos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Antihypertensive Agents); 0 (Calcium Channel Blockers); 0J48LPH2TH (Hydrochlorothiazide); 27O7W4T232 (Spironolactone); Q0MQD1073Q (Chlorthalidone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:29198636
[Au] Autor:de Almeida CLB; Cechinel-Filho V; Boeing T; Mariano LNB; Silva LMD; Andrade SF; de Souza P
[Ad] Endereço:Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC 88302-901, Brazil.
[Ti] Título:Prolonged diuretic and saluretic effect of nothofagin isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats: Role of antioxidant system and renal protection.
[So] Source:Chem Biol Interact;279:227-233, 2018 Jan 05.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Although the acute diuretic effect of nothofagin has been recently demonstrated, its effects after dose-repeated treatment have not yet been explored. For that, male Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) were orally treated, once a day, with vehicle (VEH: distilled water; 1 ml/kg), hydrochlorothiazide (HCTZ; 10 mg/kg) or nothofagin (NOT; 1 mg/kg). The cumulative diuretic index and urinary electrolytes excretion were measured each 24 h. On the last day of the experiment (7th day), urine, blood and kidney samples were collected for biochemical and molecular analyzes. The urinary volume of both NTR and SHR were significantly increased with the treatment with NOT (from the second to the seventh day of treatment), with final values reaching an increase of 56% and 82%, respectively, when compared with VEH-treated group. This effect was associated with increased levels of urinary excretion of Na and Cl , without any changes on K excretion. None of the treatments modified urinary pH or density values. Importantly, neither the NOT nor the HCTZ caused any change in body weight following the dose-repeated treatment, and also did not provoke an electrolytic disturbance. Regarding the renal analyzes, when compared with the vehicle-treated NTR group, the activity of superoxide dismutase (SOD) and the reduced glutathione (GSH) levels in kidney homogenates of the SHR group were decreased, while the generation of lipid hydroperoxides were significantly increased. The daily treatment with NOT was able to restore the GSH levels and SOD activity, as well as reduced the lipoperoxidation in the kidney homogenates obtained from SHR animals. Finally, NOT significantly augmented the levels of nitrite, a marker of nitric oxide production, in the plasma obtained from SHR group when compared with the vehicle-treated only NTR. This study revealed the prolonged diuretic and saluretic effect of nothofagin in normotensive and hypertensive rats. Our data also showed the renal protective effects of nothofagin by the improvement of antioxidative capacity, as well as by the augmented bioavailability of plasma nitric oxide in the hypertensive group.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Chalconas/farmacologia
Hipertensão/tratamento farmacológico
Rim/efeitos dos fármacos
Melastomataceae/química
Folhas de Planta/química
[Mh] Termos MeSH secundário: Animais
Chalconas/uso terapêutico
Diuréticos/farmacologia
Hidroclorotiazida/farmacologia
Masculino
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Chalcones); 0 (Diuretics); 0 (nothofagin); 0J48LPH2TH (Hydrochlorothiazide)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180103
[Lr] Data última revisão:
180103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE


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[PMID]:28763529
[Au] Autor:Song L; Maalouf NM
[Ad] Endereço:Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
[Ti] Título:24-Hour Urine Calcium in the Evaluation and Management of Nephrolithiasis.
[So] Source:JAMA;318(5):474-475, 2017 Aug 01.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Cálcio/urina
Hipercalciúria/etiologia
Nefrolitíase/urina
[Mh] Termos MeSH secundário: Adulto
Diuréticos/uso terapêutico
Seres Humanos
Hidroclorotiazida/uso terapêutico
Hipercalciúria/tratamento farmacológico
Masculino
Nefrolitíase/etiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diuretics); 0J48LPH2TH (Hydrochlorothiazide); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.7085


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[PMID]:28724547
[Au] Autor:Okada Y; Shibata S; Fujimoto N; Best SA; Levine BD; Fu Q
[Ad] Endereço:Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.
[Ti] Título:Long-term effects of a renin inhibitor versus a thiazide diuretic on arterial stiffness and left ventricular diastolic function in elderly hypertensive patients.
[So] Source:Am J Physiol Regul Integr Comp Physiol;313(4):R400-R409, 2017 Oct 01.
[Is] ISSN:1522-1490
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Arterial stiffness and cardiac function are important predictors of cardiovascular events in patients with hypertension, even with adequate blood pressure (BP) control. We evaluated whether a direct renin inhibitor, aliskiren, reduces arterial stiffness and modulates left ventricular function compared with a diuretic, hydrochlorothiazide, in elderly hypertensive patients. Twenty-one hypertensive patients [67 ± 14 (SD) yr] were randomly assigned to receive 6-mo aliskiren ( = 11) or hydrochlorothiazide ( = 10)-based therapy. We assessed ß-stiffness of the local arteries, arterial elastance ( ), and echocardiographic variables, including early ( ) and late ( ) mitral inflow velocity, deceleration time of E, early ( ') and late ( ') diastolic mitral annular velocity, and left ventricular end-systolic elastance ( ) before and after treatment. BP decreased similarly ( < 0.001) after both therapies. ß-Stiffness of the carotid artery decreased after aliskiren but increased after hydrochlorothiazide treatment (aliskiren: 6.42 ± 2.34 pre vs. 5.07 ± 1.29 post; hydrochlorothiazide: 5.05 ± 1.78 vs. 7.25 ± 2.68, = 0.001 for interaction). ß-Stiffness of the femoral and radial arteries were not different after either treatment. Different from aliskiren, decreased (73 ± 16 vs. 67 ± 14 cm/s, = 0.026), and the deceleration time was prolonged (218 ± 40 vs. 236 ± 35 ms, = 0.032) after hydrochlorothiazide therapy, whereas the / , and ' remained unchanged after both treatments. and decreased after aliskiren therapy (both < 0.05), whereas the / (ventricular-arterial coupling) was maintained after both treatments. Thus, aliskiren decreased the stiffness of carotid artery and left ventricular end-systolic elastance with maintenance of ventricular-arterial coupling without any effects on diastolic filling, while hydrochlorothiazide increased carotid arterial stiffness and slowed early diastolic filling in elderly hypertensive patients.
[Mh] Termos MeSH primário: Amidas/farmacologia
Diástole/efeitos dos fármacos
Fumaratos/farmacologia
Hidroclorotiazida/farmacologia
Hipertensão/tratamento farmacológico
Renina/antagonistas & inibidores
Inibidores de Simportadores de Cloreto de Sódio/farmacologia
Rigidez Vascular/efeitos dos fármacos
Função Ventricular Esquerda/efeitos dos fármacos
[Mh] Termos MeSH secundário: Idoso
Amidas/uso terapêutico
Anti-Hipertensivos/farmacologia
Anti-Hipertensivos/uso terapêutico
Pressão Sanguínea/efeitos dos fármacos
Pressão Sanguínea/fisiologia
Diástole/fisiologia
Ecocardiografia
Feminino
Artéria Femoral/efeitos dos fármacos
Artéria Femoral/fisiopatologia
Fumaratos/uso terapêutico
Seres Humanos
Hidroclorotiazida/uso terapêutico
Hipertensão/diagnóstico por imagem
Hipertensão/fisiopatologia
Masculino
Meia-Idade
Artéria Radial/efeitos dos fármacos
Artéria Radial/fisiopatologia
Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico
Resultado do Tratamento
Rigidez Vascular/fisiologia
Função Ventricular Esquerda/fisiologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Amides); 0 (Antihypertensive Agents); 0 (Fumarates); 0 (Sodium Chloride Symporter Inhibitors); 0J48LPH2TH (Hydrochlorothiazide); 502FWN4Q32 (aliskiren); EC 3.4.23.15 (Renin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1152/ajpregu.00125.2017


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[PMID]:28719636
[Au] Autor:Alshahrani S; Rapoport RM; Zahedi K; Jiang M; Nieman M; Barone S; Meredith AL; Lorenz JN; Rubinstein J; Soleimani M
[Ad] Endereço:Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Cincinnati, OH, United States of America.
[Ti] Título:The non-diuretic hypotensive effects of thiazides are enhanced during volume depletion states.
[So] Source:PLoS One;12(7):e0181376, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Thiazide derivatives including Hydrochlorothiazide (HCTZ) represent the most common treatment of mild to moderate hypertension. Thiazides initially enhance diuresis via inhibition of the kidney Na+-Cl- Cotransporter (NCC). However, chronic volume depletion and diuresis are minimal while lowered blood pressure (BP) is maintained on thiazides. Thus, a vasodilator action of thiazides is proposed, likely via Ca2+-activated K+ (BK) channels in vascular smooth muscles. This study ascertains the role of volume depletion induced by salt restriction or salt wasting in NCC KO mice on the non-diuretic hypotensive action of HCTZ. HCTZ (20mg/kg s.c.) lowered BP in 1) NCC KO on a salt restricted diet but not with normal diet; 2) in volume depleted but not in volume resuscitated pendrin/NCC dKO mice; the BP reduction occurs without any enhancement in salt excretion or reduction in cardiac output. HCTZ still lowered BP following treatment of NCC KO on salt restricted diet with paxilline (8 mg/kg, i.p.), a BK channel blocker, and in BK KO and BK/NCC dKO mice on salt restricted diet. In aortic rings from NCC KO mice on normal and low salt diet, HCTZ did not alter and minimally decreased maximal phenylephrine contraction, respectively, while contractile sensitivity remained unchanged. These results demonstrate 1) the non-diuretic hypotensive effects of thiazides are augmented with volume depletion and 2) that the BP reduction is likely the result of HCTZ inhibition of vasoconstriction through a pathway dependent on factors present in vivo, is unrelated to BK channel activation, and involves processes associated with intravascular volume depletion.
[Mh] Termos MeSH primário: Anti-Hipertensivos/farmacologia
Hidroclorotiazida/farmacologia
Hipovolemia/fisiopatologia
[Mh] Termos MeSH secundário: Antagonistas de Receptores de Angiotensina/farmacologia
Animais
Pressão Sanguínea/efeitos dos fármacos
Débito Cardíaco/efeitos dos fármacos
Dieta Hipossódica
Hipovolemia/metabolismo
Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo
Camundongos
Receptores de Angiotensina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiotensin Receptor Antagonists); 0 (Antihypertensive Agents); 0 (Large-Conductance Calcium-Activated Potassium Channels); 0 (Receptors, Angiotensin); 0J48LPH2TH (Hydrochlorothiazide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181376


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[PMID]:28566500
[Au] Autor:Li J; Hatano R; Xu S; Wan L; Yang L; Weinstein AM; Palmer L; Wang T
[Ad] Endereço:Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut.
[Ti] Título:Gender difference in kidney electrolyte transport. I. Role of AT receptor in thiazide-sensitive Na -Cl cotransporter activity and expression in male and female mice.
[So] Source:Am J Physiol Renal Physiol;313(2):F505-F513, 2017 Aug 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We studied gender differences in Na -Cl cotransporter (NCC) activity and expression in wild-type (WT) and AT receptor knockout (KO) mice. In renal clearance experiments, urine volume (UV), glomerular filtration rate, absolute Na (E ) and K (E ), and fractional Na (FE ) and K excretion were measured and compared at peak changes after bolus intravenous injection of hydrochlorothiazide (HCTZ; 30 mg/kg). In WT, females responded more strongly than males to HCTZ, with larger fractional increases of UV (7.8- vs. 3.4-fold), E (11.7- vs. 5.7-fold), FE (7.9- vs. 4.9-fold), and E (2.8- vs. 1.4-fold). In contrast, there were no gender differences in the responses to the diuretic in KO mice; HCTZ produced greater effects on male KO than on WT but similar effects on females. In WT, total (tNCC) and phosphorylated (pNCC) NCC protein expressions were 1.8- and 4.6-fold higher in females compared with males ( < 0.05), consistent with the larger response to HCTZ. In KO mice, tNCC and pNCC increased significantly in males to levels not different from those in females. There were no gender differences in the expression of the Na /H exchanger (NHE3) in WT; NHE3 protein decreased to similar extents in male and female KO animals, suggesting AT -mediated NHE3 expression in proximal tubules. The resulting increase in delivery of NaCl to the distal nephron may underlie increased NCC expression and activity in mice lacking the AT receptor.
[Mh] Termos MeSH primário: Angiotensina II/metabolismo
Receptor Tipo 1 de Angiotensina/metabolismo
Caracteres Sexuais
Trocadores de Sódio-Hidrogênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Diurese
Feminino
Hidroclorotiazida
Rim/metabolismo
Masculino
Camundongos Knockout
Natriurese
Fenótipo
Proteínas Serina-Treonina Quinases/metabolismo
Receptor Tipo 1 de Angiotensina/genética
Receptores de Droga/metabolismo
Simportadores de Cloreto de Sódio/metabolismo
Trocador 3 de Sódio-Hidrogênio
Membro 3 da Família 12 de Carreador de Soluto/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptor, Angiotensin, Type 1); 0 (Receptors, Drug); 0 (Slc12a3 protein, mouse); 0 (Slc9a3 protein, mouse); 0 (Sodium Chloride Symporters); 0 (Sodium-Hydrogen Exchanger 3); 0 (Sodium-Hydrogen Exchangers); 0 (Solute Carrier Family 12, Member 3); 0 (thiazide receptor); 0J48LPH2TH (Hydrochlorothiazide); 11128-99-7 (Angiotensin II); EC 2.7.1.- (Prkwnk4 protein, mouse); EC 2.7.1.- (Stk39 protein, mouse); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00087.2017


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[PMID]:28480532
[Au] Autor:Pottegård A; Hallas J; Olesen M; Svendsen MT; Habel LA; Friedman GD; Friis S
[Ad] Endereço:Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
[Ti] Título:Hydrochlorothiazide use is strongly associated with risk of lip cancer.
[So] Source:J Intern Med;282(4):322-331, 2017 Oct.
[Is] ISSN:1365-2796
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The diuretic hydrochlorothiazide is amongst the most frequently prescribed drugs in the United States and Western Europe, but there is suggestive evidence that hydrochlorothiazide use increases the risk of lip cancer. OBJECTIVES: To study the association between use of hydrochlorothiazide and squamous cell carcinoma of the lip. METHODS: We conducted a case-control study using Danish nationwide registry data. From the Cancer Registry (2004-2012), we identified 633 case patients with squamous cell carcinoma (SCC) of the lip and matched them to 63 067 population controls using a risk-set sampling strategy. Hydrochlorothiazide use (1995-2012) was obtained from the Prescription Registry and defined according to cumulative use. Applying conditional logistic regression, we calculated odds ratios (ORs) for SCC lip cancer associated with hydrochlorothiazide use, adjusting for predefined potential confounders obtained from demographic, prescription and patient registries. RESULTS: Ever-use of hydrochlorothiazide was associated with an adjusted OR for SCC lip cancer of 2.1 (95% confidence interval (CI): 1.7-2.6), increasing to 3.9 (95%CI: 3.0-4.9) for high use (≥25 000 mg). There was a clear dose-response effect (P < 0.001), with the highest cumulative dose category of hydrochlorothiazide (≥100 000 mg) presenting an OR of 7.7 (95%CI: 5.7-10.5). No association with lip cancer was seen with use of other diuretics or nondiuretic antihypertensives. Assuming causality, we estimated that 11% of the SCC lip cancer cases could be attributed to hydrochlorothiazide use. CONCLUSIONS: Hydrochlorothiazide use is strongly associated with an increased risk of lip cancer.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/induzido quimicamente
Diuréticos/efeitos adversos
Hidroclorotiazida/efeitos adversos
Neoplasias Labiais/induzido quimicamente
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Carcinoma de Células Escamosas/epidemiologia
Estudos de Casos e Controles
Dinamarca/epidemiologia
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Neoplasias Labiais/epidemiologia
Modelos Logísticos
Masculino
Meia-Idade
Sistema de Registros
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diuretics); 0J48LPH2TH (Hydrochlorothiazide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170509
[St] Status:MEDLINE
[do] DOI:10.1111/joim.12629


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[PMID]:28442491
[Au] Autor:Grimm PR; Coleman R; Delpire E; Welling PA
[Ad] Endereço:Department of Physiology, Maryland Kidney Discovery Center, University of Maryland Medical School, Baltimore, Maryland; and.
[Ti] Título:Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal Tubules.
[So] Source:J Am Soc Nephrol;28(9):2597-2606, 2017 Sep.
[Is] ISSN:1533-3450
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK). Renal expression of the constitutively active (CA)-SPAK mutant was specifically targeted to the early DCT using a DCT-driven Cre recombinase. CA-SPAK mice displayed thiazide-treatable hypertension and hyperkalemia, concurrent with NCC hyperphosphorylation. However, thiazide-mediated inhibition of NCC and consequent restoration of sodium excretion did not immediately restore urinary potassium excretion in CA-SPAK mice. Notably, CA-SPAK mice exhibited ASDN remodeling, involving a reduction in connecting tubule mass and attenuation of epithelial sodium channel (ENaC) and ROMK expression and apical localization. Blocking hyperactive NCC in the DCT gradually restored ASDN structure and ENaC and ROMK expression, concurrent with the restoration of urinary potassium excretion. These findings verify that NCC hyperactivity underlies FHHt but also reveal that NCC-dependent changes in the driving force for potassium secretion are not sufficient to explain hyperkalemia. Instead, a DCT-ASDN coupling process controls potassium balance in health and becomes aberrantly activated in FHHt.
[Mh] Termos MeSH primário: Hidroclorotiazida/farmacologia
Túbulos Renais Distais/patologia
Proteínas Serina-Treonina Quinases/metabolismo
Pseudo-Hipoaldosteronismo/metabolismo
Inibidores de Simportadores de Cloreto de Sódio/farmacologia
Membro 3 da Família 12 de Carreador de Soluto/metabolismo
[Mh] Termos MeSH secundário: Aldosterona/metabolismo
Animais
Pressão Sanguínea/efeitos dos fármacos
Canais Epiteliais de Sódio/metabolismo
Hidroclorotiazida/uso terapêutico
Túbulos Renais Distais/metabolismo
Camundongos
Natriurese/efeitos dos fármacos
Fosforilação
Potássio/urina
Canais de Potássio Corretores do Fluxo de Internalização/metabolismo
Proteínas Serina-Treonina Quinases/genética
Pseudo-Hipoaldosteronismo/tratamento farmacológico
Pseudo-Hipoaldosteronismo/genética
Pseudo-Hipoaldosteronismo/urina
Transdução de Sinais
Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Epithelial Sodium Channels); 0 (Kcnj1 protein, mouse); 0 (Potassium Channels, Inwardly Rectifying); 0 (Sodium Chloride Symporter Inhibitors); 0 (Solute Carrier Family 12, Member 3); 0J48LPH2TH (Hydrochlorothiazide); 4964P6T9RB (Aldosterone); EC 2.7.1.- (Stk39 protein, mouse); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); RWP5GA015D (Potassium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE
[do] DOI:10.1681/ASN.2016090948


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[PMID]:28388724
[Au] Autor:Tsvetov G; Hirsch D; Shimon I; Benbassat C; Masri-Iraqi H; Gorshtein A; Herzberg D; Shochat T; Shraga-Slutzky I; Diker-Cohen T
[Ad] Endereço:Institute of Endocrinology, Diabetes and Metabolism, and.
[Ti] Título:Thiazide Treatment in Primary Hyperparathyroidism-A New Indication for an Old Medication?
[So] Source:J Clin Endocrinol Metab;102(4):1270-1276, 2017 Apr 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: There is no therapy for control of hypercalciuria in nonoperable patients with primary hyperparathyroidism (PHPT). Thiazides are used for idiopathic hypercalciuria but are avoided in PHPT to prevent exacerbating hypercalcemia. Nevertheless, several reports suggested that thiazides may be safe in patients with PHPT. Objective: To test the safety and efficacy of thiazides in PHPT. Design: Retrospective analysis of medical records. Setting: Endocrine clinic at a tertiary hospital. Patients: Fourteen male and 58 female patients with PHPT treated with thiazides. Interventions: Data were compared for each patient before and after thiazide administration. Main Outcome Measures: Effect of thiazide on urine and serum calcium levels. Results: Data are given as mean ± standard deviation. Treatment with hydrochlorothiazide 12.5 to 50 mg/d led to a decrease in mean levels of urine calcium (427 ± 174 mg/d to 251 ± 114 mg/d; P < 0.001) and parathyroid hormone (115 ± 57 ng/L to 74 ± 36 ng/L; P < 0.001), with no change in serum calcium level (10.7 ± 0.4 mg/dL off treatment, 10.5 ± 1.2 mg/dL on treatment, P = 0.4). Findings were consistent over all doses, with no difference in the extent of reduction in urine calcium level or change in serum calcium level by thiazide dose. Conclusion: Thiazides may be effective even at a dose of 12.5 mg/d and safe at doses of up to 50 mg/d for controlling hypercalciuria in patients with PHPT and may have an advantage in decreasing serum parathyroid hormone level. However, careful monitoring for hypercalcemia is required.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Diuréticos/uso terapêutico
Hidroclorotiazida/uso terapêutico
Hipercalcemia/tratamento farmacológico
Hiperparatireoidismo/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Cálcio/sangue
Cálcio/urina
Diuréticos/efeitos adversos
Feminino
Seres Humanos
Hidroclorotiazida/efeitos adversos
Hipercalcemia/sangue
Hipercalcemia/urina
Hiperparatireoidismo/sangue
Hiperparatireoidismo/urina
Masculino
Meia-Idade
Hormônio Paratireóideo/urina
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diuretics); 0 (Parathyroid Hormone); 0J48LPH2TH (Hydrochlorothiazide); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170518
[Lr] Data última revisão:
170518
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-2481


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[PMID]:28356292
[Au] Autor:Frindt G; Yang L; Uchida S; Weinstein AM; Palmer LG
[Ad] Endereço:Department of Physiology and Biophysics, Weill-Cornell Medical College, New York, New York.
[Ti] Título:Responses of distal nephron Na transporters to acute volume depletion and hyperkalemia.
[So] Source:Am J Physiol Renal Physiol;313(1):F62-F73, 2017 Jul 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We assessed effects of acute volume reductions induced by administration of diuretics in rats. Direct block of Na transport produced changes in urinary electrolyte excretion. Adaptations to these effects appeared as alterations in the expression of protein for the distal nephron Na transporters NCC and ENaC. Two hours after a single injection of furosemide (6 mg/kg) or hydrochlorothiazide (HCTZ; 30 mg/kg) Na and K excretion increased but no changes in the content of activated forms of NCC (phosphorylated on residue T53) or ENaC (cleaved γ-subunit) were detected. In contrast, amiloride (0.6 mg/kg) evoked a similar natriuresis that coincided with decreased pT53NCC and increased cleaved γENaC. Alterations in posttranslational membrane protein processing correlated with an increase in plasma K of 0.6-0.8 mM. Decreased pT53NCC occurred within 1 h after amiloride injection, whereas changes in γENaC were slower and were blocked by the mineralocorticoid receptor antagonist spironolactone. Increased γENaC cleavage correlated with elevation of the surface expression of the subunit as assessed by in situ biotinylation. Na depletion induced by 2 h of furosemide or HCTZ treatment increases total NCC expression without affecting ENaC protein. However, restriction of Na intake for 10 h (during the day) or 18 h (overnight) increased the abundance of both total NCC and of cleaved α- and γENaC. We conclude that the kidneys respond acutely to hyperkalemic challenges by decreasing the activity of NCC while increasing that of ENaC. They respond to hypovolemia more slowly, increasing Na reabsorptive capacities of both of these transporters.
[Mh] Termos MeSH primário: Diuréticos/farmacologia
Canais Epiteliais de Sódio/efeitos dos fármacos
Hiperpotassemia/metabolismo
Hipovolemia/metabolismo
Néfrons/efeitos dos fármacos
Potássio/metabolismo
Sódio/metabolismo
[Mh] Termos MeSH secundário: Amilorida/farmacologia
Animais
Diuréticos/toxicidade
Canais Epiteliais de Sódio/metabolismo
Feminino
Furosemida/farmacologia
Hidroclorotiazida/farmacologia
Hiperpotassemia/sangue
Hiperpotassemia/induzido quimicamente
Hiperpotassemia/urina
Hipovolemia/sangue
Hipovolemia/induzido quimicamente
Hipovolemia/urina
Masculino
Modelos Biológicos
Néfrons/metabolismo
Fosforilação
Potássio/sangue
Potássio/urina
Ratos Sprague-Dawley
Eliminação Renal/efeitos dos fármacos
Sódio/sangue
Sódio/urina
Membro 3 da Família 12 de Carreador de Soluto/efeitos dos fármacos
Membro 3 da Família 12 de Carreador de Soluto/metabolismo
Espironolactona/farmacologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diuretics); 0 (Epithelial Sodium Channels); 0 (Scnn1g protein, rat); 0 (Slc12a3 protein, rat); 0 (Solute Carrier Family 12, Member 3); 0J48LPH2TH (Hydrochlorothiazide); 27O7W4T232 (Spironolactone); 7DZO8EB0Z3 (Amiloride); 7LXU5N7ZO5 (Furosemide); 9NEZ333N27 (Sodium); RWP5GA015D (Potassium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170331
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00668.2016



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