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Emilio A Herrera, Francisca Cifuentes-Zúñiga, Esteban Figueroa, Cristian Villanueva, Cherie Hernández, René Alegría, Viviana Arroyo, Estefania Peñaloza, Marcelo Farías, Ricardo Uauy, Paola Casanello, Bernardo J Krause
In humans, intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial programming in umbilical vessels. We aimed to determine the effects of maternal antioxidant treatment with N-acetyl cysteine (NAC) on fetal endothelial function and eNOS programming in IUGR guinea pigs. IUGR was induced by implanting ameroid constrictors on uterine arteries of pregnant guinea pigs at mid gestation, receiving half of the sows NAC in the drinking water (from day 34 until term)...
October 14, 2016: Journal of Physiology
Harry Z E Greenberg, Kazi S Jahan, Jian Shi, W-S Vanessa Ho, Anthony P Albert
The present study investigates the effect of commonly used negative and positive allosteric modulators of the calcium-sensing receptor (CaSR) on vascular reactivity. In wire myography studies, increasing [Ca(2+)]o from 1mM to 6mM induced concentration-dependent relaxations of methoxamine-induced pre-contracted rabbit mesenteric arteries, with 6mM [Ca(2+)]o producing almost complete relaxation. [Ca(2+)]o-induced relaxations were attenuated in the presence of the calcilytics Calhex-231 and NPS 2143, and abolished by the removal of the endothelium...
October 8, 2016: European Journal of Pharmacology
Michal Bencze, Michal Behuliak, Anna Vavřínová, Josef Zicha
AIMS: The goal of our study was to reveal the important mechanism(s) responsible for the enhanced contractility of isolated arteries from animals suffering genetic hypertension. MAIN METHODS: Contractile force of endothelium-denuded arteries, modulated by various interventions, was measured by wire myography. KEY FINDINGS: Spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) arteries were stimulated by norepinephrine, increased extracellular K(+) or tyramine...
October 6, 2016: Life Sciences
Sen Li, Sai-Jie Zuo, Lei Cao, Dong-Zheng Liu, San-Qi Zhang, Yong-Xiao Cao
A novel 3-benzylquinazolin-4(3H)-one derivative Z32, namely 6,7-dimethoxy-3-(3-chloro-4-(4-fluorobenzyloxy)benzyl)quinazolin-4(3H)-one was synthesized. The vasorelaxant and antihypertensive effects of Z32 and its underlying mechanisms were investigated. The following methods were used. The isometric tension of artery ring segments was recorded using an in vitro myography system. Changes in the calcium influx in mesenteric arteries were surveyed using a real-time confocal microscopy. The arterial pressure of spontaneously hypertensive rats was measured in vivo using a non-invasive tail cuff blood pressure system...
October 5, 2016: European Journal of Pharmacology
Yulong Chen, Cangbao Xu, Yahui Wei, Yaping Zhang, Ailan Cao
Resveratrol (Res) is a specific agonist of sirtuin 1, and has many cardioprotective effects. Although Res is able to relax various vascular beds, its pharmacological properties in rat superior mesenteric arteries and the underlying mechanism are not well clarified. The aim of present study was to investigate the vasorelaxant effects of Res on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro using myography. It was found that Res concentration-dependently relaxed endothelium-intact superior mesenteric artery rings pre-contracted by phenylephrine hydrochloride (Emax, 97...
October 2016: Experimental and Therapeutic Medicine
Debrabata Chanda, Jesus Prieto-Lloret, Arjun Singh, Hina Iqbal, Pankaj Yadav, Vladimir Snetkov, Philip I Aaronson
BACKGROUND AND PURPOSE: Glabridin is a major flavonoid in Glycyrrhiza glabra (licorice) root, a traditional Asian medicine. Glabridin is reported to have anti-atherogenic, anti-inflammatory and anti-nephritic properties; however its effects on vascular tone remain unexplored. EXPERIMENTAL APPROACH: We examined the effect of glabridin on rat main mesenteric artery using isometric myography and also ELISA to measure cGMP levels. KEY RESULTS: Glabridin (30μM) relaxed arteries pre-constricted with the thromboxane A2 analog U46619 (0...
September 26, 2016: Life Sciences
Ruth A Morgan, John A Keen, Brian R Walker, Patrick W F Hadoke
Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing's disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing's syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited...
2016: PloS One
Y Onetti, A P Dantas, B Pérez, A J McNeish, E Vila, F Jiménez-Altayó
AIM: Increased thromboxane A2 and peroxynitrite are hallmarks of cerebral ischaemia/reperfusion (I/R). Stimulation of thromboxane/prostaglandin receptors (TP) attenuates endothelium-derived hyperpolarization (EDH). We investigated whether EDH-type middle cerebral artery (MCA) relaxations following TP stimulation are altered after I/R and the influence of peroxynitrite. METHODS: Vascular function was determined by wire myography after TP stimulation with the thromboxane A2 mimetic 9,11-dideoxy-9α, 11α -methano-epoxy prostaglandin F2α (U46619) in MCA of Sprague Dawley rats subjected to MCA occlusion (90 min)/reperfusion (24 h) or sham operation, and in non-operated (control) rats...
September 28, 2016: Acta Physiologica
Niranjana Natarajan, Daijiro Hori, Sheila Flavahan, Jochen Steppan, Nicholas A Flavahan, Dan E Berkowitz, Jennifer L Pluznick
Short chain fatty acid (SCFA) metabolites are byproducts of gut microbial metabolism that are known to affect host physiology via GPCRs. We previously showed that an acute SCFA bolus decreases blood pressure (BP) in anesthetized mice, an effect mediated via Gpr41. In this study, our aims were to identify the cellular localization of Gpr41 and to determine its role in BP regulation. We localized Gpr41 to the vascular endothelium using RT-PCR: Gpr41 is detected in intact vessels, but is absent from denuded vessels...
September 23, 2016: Physiological Genomics
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
Adam P Harvey, Augusto Montezano, Khai C Wong, Katie Y Hood, Rheure Alves-Lopes, Graziela S Ceravolo, Chihiro Yabe-Nishimura, Delyth Graham, Rhian M Touyz
OBJECTIVE: In hypertension, the vasculature undergoes alterations that resemble those seen in aging. The involvement of aldosterone and Noxs in the mechanisms underlying age-associated vascular damage is unclear. We postulated that aging-like changes in the vasculature is amplified in hypertension due to increased aldosterone-induced Nox-redox signalling. DESIGN AND METHOD: We assessed vascular aging in arteries from adult WKY (18 weeks), aged WKY (52 weeks) and adult stroke-prone spontaneously hypertensive (SHRSP) rats...
September 2016: Journal of Hypertension
Lingran Kong, Chengchao Ruan, Pingjin Gao
OBJECTIVE: Inflammatory processes plays a pivotal role in pathogenesis of hypertension. Previous study have indicated that A2A receptor is closely related with immunogenic anti-inflammation process. The present study aimed to elucidate whether the activation of A2A receptor is involved in the regulation of hypertension-induced cardiovascular consequence via regulating immunoresponse. DESIGN AND METHOD: Deoxycorticosterone acetat (DOCA)-salt hypertensive mice were injected intraperitoneally with specific A2A receptor agonist (CGS21680) or antagonist (istradefylline) or PBS respectively...
September 2016: Journal of Hypertension
Pierre Paradis, Suellen C Coelho, Sofiane Ouerd, Júlio C Fraulob-Aquino, Stefan Offermanns, Ernesto L Schiffrin
OBJECTIVE: The mechanisms of blood pressure (BP) regulation by endothelin (ET)-1 produced by endothelial cells are complex and remain unclear. Recently, we developed a transgenic mouse with tamoxifen-inducible endothelium-restricted human ET-1 overexpression (ieET-1) using Cre/loxP technology. ieET-1 mice exhibited a BP increase after three weeks of induction in an ET type A receptor-dependent manner, in absence of evident vascular injury. It is unknown whether long-term exposure to ET-1 overexpression results in persistent BP elevation and vascular injury...
September 2016: Journal of Hypertension
Francisco J Rios, Katie Y Hood, A Karvey, Karla B Neves, Panagiota Anyfanti, Ryszard Nosalski, Livia L Camargo Ll, Augusto C Montezano, Rhian M Touyz
OBJECTIVE: TRPM7 is cation channel with intrinsic kinase activity important for cellular Mg homeostasis. We recently showed that TRPM7-kinase plays a role in aldosterone-mediated vascular effects and inflammation. Here we explored the putative role of TRPM7-kinase in cardiac fibrosis and vascular function in aldosterone-induced hypertension in mice. DESIGN AND METHOD: Wild-type (WT) or heterozygote TRPM7-kinase domain (TRPM7+/-) mice were treated with infused aldosterone (600 μg/Kg/day) and NaCl 1% in drinking water (aldo/salt) for 4 weeks...
September 2016: Journal of Hypertension
Pierre Paradis, Sofiane Ouerd, Noureddine Idris-Khodja, Michelle Trindade, Suellen C Coelho, Karin A Jandeleit-Dahm, Ernesto L Schiffrin
OBJECTIVE: The prognosis of type-1 diabetes remains poor and is primarily related to the increased risk of vascular complications. Overproduction of reactive oxygen species by NADPH oxidase (NOX) is believed to play an important role in diabetes-related vascular injury. NOX1 may play a role in the macrovascular disease, whereas NOX4 may have protective actions. Nevertheless, their role in diabetic microangiopathy is less well understood. We hypothesized that deletion of Nox1 would prevent diabetes-induced endothelial dysfunction and vascular remodeling of small arteries whereas Nox4 would exaggerate vascular injury...
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
Deepesh Pandey, Daijiro Tori, Yohei Nomura, Dan Berkowitz, Lewis Romer
OBJECTIVE: Kruppel Like Factor 15 (KLF15) has recently been shown to be critical for activation of proinflammatory processes in vascular smooth muscle and atherogenesis. Although KLF15 is abundantly expressed in vascular endothelium there is a significant lack of knowledge regarding the role of KLF15 in the regulation of vascular endothelial function. Here we tested the hypothesis that KLF15 is a critical regulator of Arg2 transcription in hypoxia exposed human pulmonary microvascular endothelial cells (HPMEC) and that it plays critical role in pathogenesis of pulmonary hypertension (PHTN)...
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
Antonio Lisboa, Rodolfo Melaré, Junia R B Franco, Carolina V Bis, Marta Gracia, Luis A Ponce-Soto, Sérgio Marangoni, Léa Rodrigues-Simioni, Maria Alice da Cruz-Höfling, Thalita Rocha
Neuromuscular preparations exposed to B. marajoensis venom show increases in the frequency of miniature end-plate potentials and twitch tension facilitation followed by presynaptic neuromuscular paralysis, without evidences of muscle damage. Considering that presynaptic toxins interfere into the machinery involved in neurotransmitter release (synaptophysin, synaptobrevin, and SNAP25 proteins), the main objective of this communication is to analyze, by immunofluorescence and western blotting, the expression of the synaptic proteins, synaptophysin, synaptobrevin, and SNAP25 and by myography, light, and transmission electron microscopy the pathology of motor nerve terminals and skeletal muscle fibres of chick biventer cervicis preparations (CBC) exposed in vitro to BmjeTX-I and BmjeTX-II toxins from B...
2016: Biochemistry Research International
Christopher P Stanley, William H Hind, Christina Tufarelli, Saoirse E O'Sullivan
The endocannabinoid anandamide (AEA) causes vasorelaxation in animal studies. Although circulating AEA levels are increased in many pathologies, little is known about its vascular effects in humans. The aim of this work was to characterise the effects of AEA in human arteries. Ethical approval was granted to obtain mesenteric arteries from patients (n=31) undergoing bowel resection. Wire myography was used to probe the effects and mechanisms of action of AEA. RT-PCR was used to confirm the presence of receptor mRNA in human aortic endothelial cells (HAECs) and intracellular signalling proteins were measured using multiplex technology...
September 12, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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