Vascular pharmacology
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Vascular pharmacology · Sep 2015
Tubastatin A suppresses renal fibrosis via regulation of epigenetic histone modification and Smad3-dependent fibrotic genes.
Inflammation and fibrosis are implicated in the pathogenesis of hypertensive kidney damage. We previously demonstrated that a nonspecific histone deacetylase (HDAC) inhibitor attenuates cardiac fibrosis in deoxycorticosterone acetate-salt hypertensive rats, which induces HDAC6 protein and enzymatic activity. However, the HDAC inhibitor's effect and mechanism have not yet been demonstrated. ⋯ We also demonstrated for the first time, to our knowledge, that acetylation of collagen type I can be regulated by HDAC6/p300 acetyltransferase. The chromatin immunoprecipitation assay revealed that the HDAC6 inhibitor suppressed TGF-β-induced acetylated histone H4 or phospho-Smad2/3 to Smad3 binding elements in the fibrosis-associated gene promoters including collagen type I. These results suggest that HDAC6 may be a valuable therapeutic target for the treatment of hypertension-induced kidney fibrosis and inflammation.
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Vascular pharmacology · Apr 2014
Reprint of "Intra-aortic balloon counterpulsation--basic principles and clinical evidence".
Intra-aortic balloon pump (IABP) counterpulsation has been the most widely used left ventricular assist device for nearly five decades. Due to diastolic inflation and systolic deflation, coronary blood flow is increased and afterload decreased translating into augmentation of oxygen supply and lowering of oxygen demand. However, IABP may be associated with serious complications, including major bleeding, stroke, local and systemic infections and vascular complications. ⋯ Further, prophylactic IABP use is frequently performed in patients at high risk for hemodynamic instability undergoing elective percutaneous coronary intervention or coronary artery bypass graft surgery. Current evidence, however, does not fully support routine use of IABP in these settings. This review focuses on the basic principles of IABP and discusses current evidence.
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Vascular pharmacology · Mar 2014
Endothelial nitric oxide synthase activation through obacunone-dependent arginase inhibition restored impaired endothelial function in ApoE-null mice.
Endothelial arginase constrains the activity of endothelial nitric oxide synthase (eNOS) by substrate depletion and reduces nitric oxide bioavailability. During the screening course of arginase inhibitor, we found obacunone as an arginase inhibitor. We tested the hypothesis that obacunone regulates vascular endothelial NO production. ⋯ The dose-dependent vasorelaxant response to Ach was reduced in the aortic vessels of ApoE-/- mice fed a high-cholesterol diet. Obacunone incubation increased vasorelaxation to the level of a WT mouse, although the endothelium-independent response to sodium nitroprusside was identical among the groups. Therefore, obacunone may help treat cardiovascular diseases derived from endothelial dysfunction and may be useful for designing pharmaceutical compounds.
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Vascular pharmacology · Feb 2014
ReviewIntra-aortic balloon counterpulsation - basic principles and clinical evidence.
Intra-aortic balloon pump (IABP) counterpulsation has been the most widely used left ventricular assist device for nearly five decades. Due to diastolic inflation and systolic deflation, coronary blood flow is increased and afterload decreased translating into augmentation of oxygen supply and lowering of oxygen demand. However, IABP may be associated with serious complications, including major bleeding, stroke, local and systemic infections and vascular complications. ⋯ Further, prophylactic IABP use is frequently performed in patients at high risk for hemodynamic instability undergoing elective percutaneous coronary intervention or coronary artery bypass graft surgery. Current evidence, however, does not fully support routine use of IABP in these settings. This review focuses on the basic principles of IABP and discusses current evidence.
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Vascular pharmacology · Sep 2013
ReviewThe new oral anticoagulants in atrial fibrillation: once daily or twice daily?
The new anticoagulants (NOACs) tested for prevention or treatment of venous thromboembolism (VTE), stroke prevention in atrial fibrillation (AF), and acute coronary syndromes (ACS) differ in bioavailability, metabolism, route of excretion and interaction with other drugs, but have remarkably similar pharmacokinetics, with very similar half lives. However the choice of dosing regimens in different clinical conditions has been different for the various NOACs, and has been established on the basis of widely different considerations, including the clinical setting (venous versus arterial thrombosis), the indications (prophylaxis versus treatment), the likelihood of concomitant antiplatelet drugs, and marketing opportunities; these latter were based on the knowledge that patients' compliance is generally better with once daily than with twice daily dosing. ⋯ Higher rates of bleeding have been also reported with the twice daily versus once daily dosing of darexaban in a phase II study in ACS. These results may lead to a rethinking on the pathophysiology of bleeding in the setting of anticoagulation.