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arterial vasodilators

Katarina E A Nostell, Sanna S Lindåse, Johan T Bröjer
BACKGROUND: Insulin resistance (IR) in humans is related to hypertension and impaired vasodilation. Insulin administration has been shown to lower blood pressure both in insulin resistant as well as in insulin sensitive individuals. The aim of the study was to investigate the association between insulin sensitivity and alterations in blood pressure in healthy horses before and after a euglycemic-hyperinsulinemic clamp (EHC). A 3-h EHC was performed in 13 healthy horses (11 mares, 2 geldings)...
October 20, 2016: Acta Veterinaria Scandinavica
Joshua A Beckman, Allison B Goldfine, Jane A Leopold, Mark A Creager
Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione-peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled crossover trial in 26 subjects with either type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg orally twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 weeks duration, with a 4 week washout between. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced-to-oxidized glutathione...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Jay S Naik, Jessica M Osmond, Benjimen R Walker, Nancy L Kanagy
Hydrogen sulfide (H2S) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine γ-lyase and 3-mercaptopyruvate sulfurtansferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous H2S production and are required for H2S-induced dilation. However, the signal transduction pathway activated by H2S within EC has not been elucidated. TRPV4 and large conductance Ca(2+)-activated K channels (BK channels) are expressed in EC. H2S-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Ning Xia, Huige Li
Under physiological conditions, perivascular adipose tissue (PVAT) attenuates agonist-induced vasoconstriction by releasing vasoactive molecules including hydrogen peroxide, angiotensin 1-7, adiponectin, methyl palmitate, hydrogen sulfide, nitric oxide (NO) and leptin. This anticontractile function of PVAT is lost under conditions of obesity. The central mechanism underlying PVAT dysfunction in obesity is likely to be an "obesity triad" (consisting of PVAT hypoxia, inflammation and oxidative stress) that leads to dysregulation of PVAT-derived vasoregulators...
October 20, 2016: British Journal of Pharmacology
Mais M Aljunaidy, Jude S Morton, Christy-Lynn Cooke, Sandra T Davidge
Intrauterine growth restriction (IUGR) is a common pregnancy complication and is a leading cause of fetal morbidity and mortality. Placental hypoxia contributes to adverse fetal consequences, including IUGR. Exposing pregnant rats to hypoxia can lead to IUGR; however, assessment of maternal vascular function in a rat model of hypoxia, and the mechanisms that may contribute to adverse pregnancy outcomes, has not been extensively studied. We hypothesized that exposing pregnant rats to hypoxia will affect maternal systemic vascular function and increase the uterine artery resistance index (RI), which will be associated with IUGR...
October 19, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Xinlei Song, Shu Zhang, Yanna Cheng, Ting Zhao, Qianqian Lian, Lu Lu, Fengshan Wang
OBJECTIVES: To evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model. SETTING: Laboratory. SUBJECTS: Male Wistar rats. DESIGN: Prospective study. INTERVENTIONS: Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids...
November 2016: Critical Care Medicine
Mayank Sardana, Matthew Moll, Harrison W Farber
Management of pulmonary arterial hypertension (PAH) remains challenging even in the contemporary era. Intravenous prostacyclin therapy, while associated with decreased mortality, has practical limitations and requires significant lifestyle modifications. The recently approved long-acting oral IP prostacyclin receptor agonist for treatment of PAH, selexipag, is a non-prostanoid agent that vasodilates, impacts remodeling (anti-proliferative), reduces endothelial cell dysfunction, inhibits platelet aggregation (anti-thrombotic), and increases right heart inotropy...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Rachel Wong, Rhenan Nealon, Daniel Raederstorff, Peter Howe
OBJECTIVE: Having shown that resveratrol consumption can improve flow mediated dilation of the brachial artery, we tested its effects on CVR to hypercapnia in adults with T2DM, a risk population for cerebrovascular disease and cognitive impairments. DESIGN AND METHOD: In a double-blind crossover trial, 34 adults with T2DM consumed 0, 75, 150 and 300 mg of synthetic trans-resveratrol (one dose per week in random order). Before and 1-2 hr after dosing, transcranial Doppler ultrasound was used to assess CVR to a hypercapnic stimulus (breathing Carbogen gas for 3 min) in the middle (MCA) and posterior (PCA) cerebral arteries...
September 2016: Journal of Hypertension
Pierre Paradis, Tlili Barhoumi, Muhammad Oneeb Rehman Mian, Julio C Fraulob-Aquino, Asia Rehman, Nourredine Idris-Khodja, Ernesto L Schiffrin
OBJECTIVE: Matrix metalloproteinase 2 (MMP2) is involved in cardiovascular disease. Whether MMP2 plays a role in hypertension and vascular damage is unknown. We hypothesized that Mmp2 knockout will prevent angiotensin (Ang) II-induced hypertension and vascular injury. DESIGN AND METHOD: Mmp2 knockout (Mmp2) and wild-type (WT) mice were infused with Ang II (1000 ng/kg/min, SC) for 14 days. Systolic blood pressure (SBP) was measured by telemetry, and mesenteric artery (MA) endothelial function and vascular remodeling by pressurized myography...
September 2016: Journal of Hypertension
Sophie Saxton, Sarah Withers, Jacqueline Ohanian, Anthony Heagerty
OBJECTIVE: Perivascular adipose tissue (PVAT) exerts an anti-contractile effect vital to regulating blood pressure. Evidence suggests that the sympathetic nervous stimulation of PVAT triggers the release of anti-contractile factors via activation of β3-adrenoceptors. Therefore it was decided to examine β3-adrenoceptor function in obesity. DESIGN AND METHOD: Electrical field stimulation (EFS) of healthy and obese mouse mesenteric arteries (<200 μm, +/-PVAT) were characterised using wire myography (0...
September 2016: Journal of Hypertension
William C Cushman
Beginning with the Veterans Administration (VA) Cooperative Hypertension Study of the 1960 s, blood pressure (BP) lowering with antihypertensive medications has been shown to reduce major cardiovascular (CV) outcomes, including coronary heart disease, stroke, heart failure (HF) and CV and all-cause mortality in randomized controlled CV outcome trials. Multiple drugs were usually required in these trials to lower BP in treated participants. Medication regimens in the early trials, including the VA trial, included a thiazide-type diuretic (TTD) as initial therapy...
September 2016: Journal of Hypertension
Bin Wang, Qianqian Sun, Yingsha Li, Peng Li, Weijie Xia, Daoyan Liu, Zhiming Zhu
OBJECTIVE: Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to improve metabolic status in animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human, especially in prehypertensive participants. DESIGN AND METHOD: In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on metabolic parameters, such as blood pressure (BP) levels, carotid intima-media thickness (IMT), ankle brachial index (ABI)/toe brachial index (TBI), BMI and biochemical parameters in prehypertensive participants...
September 2016: Journal of Hypertension
Ben Clark, Sarah Withers, Anthony Heagerty
OBJECTIVE: Resistance arteries significantly contribute to peripheral vascular resistance, and also determine insulin-sensitivity by controlling blood flow to skeletal muscle. Increased microvascular tone therefore facilitates the development of hypertension and insulin-resistance. Surrounding most blood vessels, perivascular adipose tissue (PVAT) exerts a vasorelaxant 'anti-contractile' effect. Few studies on skeletal muscle resistance arteries have investigated this vasorelaxant effect and the role of insulin...
September 2016: Journal of Hypertension
Karima Ait-Aissa, Joseph Hockenberry, David Gutterman, Aron Geurts, Andreas Beyer
OBJECTIVE: Flow mediated dilation (FMD) is the most physiological relevant form of endothelial-mediated vasodilation. Our laboratory has previously shown that telomerase, a ribo-nucleoprotein that counteracts telomere shortening, has a protective effect on endothelial function under conditions of oxidative stress in the human microcirculation. In the presence of coronary artery disease, decreased telomerase activity contributes to a shift in the mediator of FMD from atheroprotective nitric oxide (NO) to pro-inflammatory and atherogenic hydrogen peroxide (H2O2)...
September 2016: Journal of Hypertension
Anthony Heagerty
There is now a considerable body of evidence to suggest that the fat cells that surround blood vessels (perivascular adipose tissue, PVAT) can influence profoundly arterial tone by releasing vasodilator adipokines which can act locally in a paracrine fashion. In healthy lean individuals the primary vasodilator released appears to be adiponectin and there is a complex interation between autonomic nerve firing in PVAT and the release of nitric oxide from adipocytes and an increased bioavailability of adiponectin...
September 2016: Journal of Hypertension
P Meimoun, J Clerc, D Ardourel, U Djou, S Martis, T Botoro, F Elmkies, H Zemir, A Luycx-Bore, J Boulanger
To test the usefulness of non-invasive coronary flow reserve (CFR) by transthoracic Doppler echocardiography by comparison to invasive fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR), a new vasodilator-free index of coronary stenosis severity, in patients with left anterior descending artery (LAD) stenosis of intermediate severity (IS) and stable coronary artery disease. 94 consecutive patients (mean age 68 ± 10 years) with angiographic LAD stenosis of IS (50-70 % diameter stenosis), were prospectively studied...
October 17, 2016: International Journal of Cardiovascular Imaging
Ferruh Artunc, Erwin Schleicher, Cora Weigert, Andreas Fritsche, Norbert Stefan, Hans-Ulrich Häring
Insulin resistance is a systemic disorder that affects many organs and insulin-regulated pathways. The disorder is characterized by a reduced action of insulin despite increased insulin concentrations (hyperinsulinaemia). The effects of insulin on the kidney and vasculature differ in part from the effects on classical insulin target organs. Insulin causes vasodilation by enhancing endothelial nitric oxide production through activation of the phosphatidylinositol 3-kinase pathway. In insulin-resistant states, this pathway is impaired and the mitogen-activated protein kinase pathway stimulates vasoconstriction...
October 17, 2016: Nature Reviews. Nephrology
Natasha M Rogers, Maryam Sharifi-Sanjani, Mingyi Yao, Kedar Ghimire, Raquel Bienes-Martinez, Stephanie M Mutchler, Heather E Knupp, Jeffrey Baust, Enrico M Novelli, Mark Ross, Claudette St Croix, Johannes C Kutten, Caitlin A Czajka, John C Sembrat, Mauricio Rojas, David Labrousse-Arias, Timothy N Bachman, Rebecca R Vanderpool, Brian S Zuckerbraun, Hunter C Champion, Ana L Mora, Adam C Straub, Richard A Bilonick, Maria J Calzada, Jeffrey S Isenberg
AIMS: Thrombospondin-1 (TSP1) is a ligand for CD47 and TSP1(-/-) mice are protected from pulmonary hypertension (PH). We hypothesized the TSP1-CD47 axis is upregulated in human PH and promotes pulmonary arterial vasculopathy. METHODS AND RESULTS: We analyzed the molecular signature and functional response of lung tissue and distal pulmonary arteries (PAs) from individuals with (n=23) and without (n=16) PH. Compared to controls, lungs and distal PAs from PH patients showed induction of TSP1-CD47 and endothelin-1/endothelin A receptor (ET-1/ETA) protein and mRNA...
October 13, 2016: Cardiovascular Research
Takashi Owada, Hiroyuki Yamauchi, Shu-Ichi Saitoh, Shunsuke Miura, Hirofumi Machii, Yasuchika Takeishi
BACKGROUND: Senescence is a major factor that increases oxidative stress in mitochondria, which contributes toward the pathogenesis of heart disease. However, the effect of antioxidant therapy on cardiac mitochondria in aged-cardiac performance remains elusive. OBJECTIVES: We postulated that the mitochondrial targeting of superoxide scavenging would have benefits in the aged heart. METHODS AND RESULTS: Generation of superoxide in the mitochondria and nicotinamide adenine dinucleotide phosphate oxidase activity increased in the heart of old mice compared with that in young mice...
October 12, 2016: Coronary Artery Disease
Frederic Pastouret, Lucia Cardozo, Jan Lamote, Ronald Buyl, Pierre Lievens
BACKGROUND A whole-body vibration technique delivered in a horizontal position through a massage mattress was introduced in 2007. The present study analyzed the effects of different exposure periods to these vibrations on microcirculation of mice. MATERIAL AND METHODS Different periods of vibrations (30Hz) were locally delivered in a horizontal position on the external abdominal skin in 3 randomized groups of mice (N=42). The 3 groups receiving vibrations were compared to an untreated control group (N=14). The 3 experimental groups received 3, 6, and 10 min of vibrations...
October 14, 2016: Medical Science Monitor Basic Research
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