Search results for "Cardiovascular Pharmacology"
showing 10 items of 10 documents
Aging Negatively Affects Estrogens-Mediated Effects on Nitric Oxide Bioavailability by Shifting ERα/ERβ Balance in Female Mice
2011
AIMS: Aging is among the major causes for the lack of cardiovascular protection by estrogen (E2) during postmenopause. Our study aims to determine the mechanisms whereby aging changes E2 effects on nitric oxide (NO) production in a mouse model of accelerated senescence (SAM). METHODS AND RESULTS: Although we found no differences on NO production in females SAM prone (SAMP, aged) compared to SAM resistant (SAMR, young), by either DAF-2 fluorescence or plasmatic nitrite/nitrate (NO2/NO3), in both cases, E2 treatment increased NO production in SAMR but had no effect in SAMP. Those results are in agreement with changes of eNOS protein and gene expression. E2 up-regulated eNOS expression in SAMR…
11,12-EET Stimulates the Association of BK Channel α and β1 Subunits in Mitochondria to Induce Pulmonary Vasoconstriction
2012
In the systemic circulation, 11,12-epoxyeicosatrienoic acid (11,12-EET) elicits nitric oxide (NO)- and prostacyclin-independent vascular relaxation, partially through the activation of large conductance Ca(2+)-activated potassium (BK) channels. However, in the lung 11,12-EET contributes to hypoxia-induced pulmonary vasoconstriction. Since pulmonary artery smooth muscle cells also express BK channels, we assessed the consequences of BKβ(1) subunit deletion on pulmonary responsiveness to 11,12-EET as well as to acute hypoxia. In buffer-perfused mouse lungs, hypoxia increased pulmonary artery pressure and this was significantly enhanced in the presence of NO synthase (NOS) and cyclooxygenase (…
The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model b…
2014
Objective In diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress. Methods Type I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection empagliflozin (10 and 30 mg/kg/d) was adminis…
Anti-Hypotensive Treatment and Endothelin Blockade Synergistically Antagonize Exercise Fatigue in Rats under Simulated High Altitude
2013
Rapid ascent to high altitude causes illness and fatigue, and there is a demand for effective acute treatments to alleviate such effects. We hypothesized that increased oxygen delivery to the tissue using a combination of a hypertensive agent and an endothelin receptor A antagonist drugs would limit exercise-induced fatigue at simulated high altitude. Our data showed that the combination of 0.1 mg/kg ambrisentan with either 20 mg/kg ephedrine or 10 mg/kg methylphenidate significantly improved exercise duration in rats at simulated altitude of 4,267 m, whereas the individual compounds did not. In normoxic, anesthetized rats, ephedrine alone and in combination with ambrisentan increased heart…
Cyclosporine A Impairs the Macrophage Reverse Cholesterol Transport in Mice by Reducing Sterol Fecal Excretion
2012
Despite the efficacy in reducing acute rejection events in organ transplanted subjects, long term therapy with cyclosporine A is associated with increased atherosclerotic cardiovascular morbidity. We studied whether this drug affects the antiatherogenic process of the reverse cholesterol transport from macrophages in vivo. Cyclosporine A 50 mg/kg/d was administered to C57BL/6 mice by subcutaneous injection for 14 days. Macrophage reverse cholesterol transport was assessed by following [(3)H]-cholesterol mobilization from pre-labeled intraperitoneally injected macrophages, expressing or not apolipoprotein E, to plasma, liver and feces. The pharmacological treatment significantly reduced the …
Pre-Infarction Angina and Outcomes in Non-ST-Segment Elevation Myocardial Infarction: Data from the RICO Survey
2012
BACKGROUND: The presence of pre-infarction angina (PIA) has been shown to confer cardioprotection after ST-segment elevation myocardial infarction (STEMI). However, the clinical impact of PIA in non-ST-segment elevation myocardial infarction (NSTEMI) remains to be determined. METHODS AND RESULTS: From the obseRvatoire des Infarctus de Côte d'Or (RICO) survey, 1541 consecutive patients admitted in intensive care unit with a first NSTEMI were included. Patients who experienced chest pain <7 days before the episode leading to admission were defined as having PIA and were compared with patients without PIA. Incidence of in-hospital ventricular arrhythmias (VAs), heart failure and 30-day mortali…
Diminished neurogenic femoral artery vasoconstrictor response in a Zucker obese rat model: differential regulation of NOS and COX derivatives.
2014
Objective: Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR) by examining cross-talk between endothelial and neural factors. Methods and Results: Arterial preparations from lean (LZR) and OZR were subjected to electrical field stimulation (EFS) on basal tone. Nitric oxide synthase (NOS) and cyclooxygenase (COX) isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition …
Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.
2013
Context and Objective Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution. Design and Participants A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l) and a baseline HDL-cholesterol of 64±15 mg/dl (1.7±0.4 mmol/l). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24) or their combination (n = 24) for 14 days. Blood was drawn before and after the treatment period. HDL subc…
Molecular modeling in cardiovascular pharmacology: Current state of the art and perspectives.
2021
Abstract Molecular modeling in pharmacology is a promising emerging tool for exploring drug interactions with cellular components. Recent advances in molecular simulations, big data analysis, and artificial intelligence (AI) have opened new opportunities for rationalizing drug interactions with their pharmacological targets. Despite the obvious utility and increasing impact of computational approaches, their development is not progressing at the same speed in different fields of pharmacology. Here, we review current in silico techniques used in cardiovascular diseases (CVDs), cardiological drug discovery, and assessment of cardiotoxicity. In silico techniques are paving the way to a new era…
Rac1-Regulated Endothelial Radiation Response Stimulates Extravasation and Metastasis That Can Be Blocked by HMG-CoA Reductase Inhibitors
2011
Radiotherapy (RT) plays a key role in cancer treatment. Although the benefit of ionizing radiation (IR) is well established, some findings raise the possibility that irradiation of the primary tumor not only triggers a killing response but also increases the metastatic potential of surviving tumor cells. Here we addressed the question of whether irradiation of normal cells outside of the primary tumor augments metastasis by stimulating the extravasation of circulating tumor cells. We show that IR exposure of human endothelial cells (EC), tumor cells (TC) or both increases TC-EC adhesion in vitro. IR-stimulated TC-EC adhesion was blocked by the HMG-CoA reductase inhibitor lovastatin. Glycyrr…