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Chlorthalidone: mechanisms of action and effect on cardiovascular events.
Curr Hypertens Rep
October 2013
UCONN School of Medicine and St. Vincent's Medical Center, 2800 Main Street, Bridgeport, CT, 06606, USA,
How chlorthalidone (CTDN) reduces risk for cardiovascular events (CVEs) can be considered in light of its ability to lower blood pressure (BP) and its non-BP related, pleiotropic effects. The mechanism by which CTDN lowers BP is unclear but may include alterations in whole body regulation and vasodilatory actions on vasculature, possibly mediated via its inhibitory effects on carbonic anhydrase. Additionally, CTDN has potentially beneficial, non-BP related, pleiotropic effects that include improvements in endothelial function, anti-platelet activity, and oxidative status.
View Article and Find Full Text PDFDoxazosin induces activation of GADD153 and cleavage of focal adhesion kinase in cardiomyocytes en route to apoptosis.
Cardiovasc Res
July 2006
Unidad de Investigación del Servicio de Cardiología, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Objective: The alpha 1-adrenoreceptor blocker doxazosin, which in the ALLHAT trial was associated with a greater risk of heart failure than the diuretic chlorthalidone, induces the apoptosis of human and murine cardiomyocytes regardless of alpha 1-adrenoreceptor blockade. We aimed to throw light on the mechanism of this process.
Methods: Murine cardiomyocytes (HL-1) and primary cultures of human and neonatal rat cardiomyocytes were treated with 25 micromol/L doxazosin for between 0.
How should patients treated with alpha-blockers be followed? Insights from an ambulatory blood pressure monitoring database.
J Hypertens
May 2006
Department of Internal Medicine, Hadassah - Hebrew University Medical Center, Mount-Scopus Campus, Jerusalem 91240, Israel.
Objective: Adrenergic alpha-antagonists have been suggested to confer lesser protection, compared to diuretics, when used as first agents for hypertension. While differences in clinic blood pressure may be partly responsible, this inferiority is unexpected in light of the metabolic advantages of alpha-blockade. The aim of this study was to evaluate the relationship between use of alpha-blockers and blood pressure dipping.
View Article and Find Full Text PDFCerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials.
J Am Coll Cardiol
April 2004
Hôpital Sud, Amiens Cedex I, France.
Based on the Medical Research Council study, Brown and Brown hypothesized in 1986 that angiotensin II could protect against strokes by causing vasoconstriction of the proximal cerebral arteries, thereby preventing Charcot-Bouchard aneurysms from rupturing. In light of this hypothesis, we evaluated the cerebroprotective effects of various drug classes in recent double-blinded, prospective, randomized trials, such as SHEP, PATS, CAPPP, HOPE, PROGRESS, INSIGHT, NORDIL, LIFE, SCOPE, ANBP2, and ALLHAT. Drugs that activate the AT2 receptors, such as diuretics, calcium antagonists, and angiotensin receptor blockers (ARBs), were consistently more beneficial for stroke reduction than drugs devoid of such activation, such as beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, despite an equal fall in arterial pressure (at least in patients with a low incidence of cardiac complications).
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