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(NOS)and(nitric oxide synthase)

Naoto Fujii, Brendan D McNeely, Glen P Kenny
β-adrenergic receptor agonists such as isoproterenol can induce cutaneous vasodilatation and sweating in humans, however, the mechanisms underpinning this response remains unresolved. We evaluated the hypotheses that 1) nitric oxide synthase (NOS) contributes to β-adrenergic cutaneous vasodilatation, whereas cyclooxygenase (COX) limits the vasodilatation, and 2) COX contributes to β-adrenergic sweating. In 10 young males (25 ± 5 years), cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal forearm skin sites infused with 1) lactated Ringer's (control), 2) 10 mm L -NNA, a non-specific NOS inhibitor, 3) 10 mM ketorolac, a non-specific COX inhibitor, or 4) a combination of L -NNA and ketorolac...
October 24, 2016: Journal of Physiology
Jing Ke, Rui Wei, Fei Yu, Jingjing Zhang, Tianpei Hong
Glucagon-like peptide-1 (GLP-1) and its analogues have a beneficial role in cardiovascular system. Here, we aimed to investigate whether liraglutide, a GLP-1 analogue, modulated angiogenesis impaired by palmitic acid (PA) in cultured human umbilical vein endothelial cells (HUVECs). Cells were incubated with liraglutide (3-100 nmol/L) in the presence of PA (0.5mmol/L), and endothelial tube formation was observed and quantified. The protein levels of signaling molecules were analyzed and the specific inhibitors were used to identify the signaling pathways through which liraglutide affected angiogenesis...
October 21, 2016: Peptides
Nikolaos Pitsikas
Close to 1% of the world population suffer from schizophrenia. Current medications for this chronic mental disorder have greatly improved treatment over the last half century or more, but, the newer atypical antipsychotics have proven to be disappointing, and enormous challenges remain. The negative symptoms and cognitive dysfunction in schizophrenia which greatly affect overall morbidity call for better treatments. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, is involved in the pathogenesis of schizophrenia, so excessive NO production might contribute to the pathology...
2016: Current Medicinal Chemistry
Félix Javier Jiménez-Jiménez, Hortensia Alonso-Navarro, María Trinidad Herrero, Elena García-Martín, José A G Agúndez
BACKGROUND: The pathogenesis of Parkinson's disease (PD) is not fully understood. Together with some important physiological functions in the Central Nervous System (CNS), nitric oxide (NO) can have both, neuroprotective or neurotoxic actions, depending on its redox state. An important body of evidence suggests the involvement of NO in many of the processes leading to neurodegeneration in several neurological disorders including PD. OBJECTIVE: The main aim of this review is to update the data regarding the possible involvement of NO in the pathogenesis of PD...
2016: Current Medicinal Chemistry
Albert W Girotti
Nitric oxide (NO) produced by nitric oxide synthase (NOS) enzymes is a free radical molecule involved in a wide variety of normophysiologic and pathophysiologic processes. Included in the latter category are cancer promotion, progression, and resistance to therapeutic intervention. Animal tumor photodynamic therapy (PDT) studies several years ago revealed that endogenous NO can reduce PDT efficacy and that NOS inhibitors can alleviate this. Until relatively recently, little else was known about this anti-PDT effect of NO, including: (a) the underlying mechanisms; (b) type(s) of NOS involved; and (c) whether active NO was generated in vascular cells, tumor cells, or both...
October 20, 2016: Cancers
R Rehakova, J Klimentova, M Cebova, A Barta, Z Matuskova, P Labas, O Pechanova
Deuterium-depleted water (DDW) has a lower concentration of deuterium than occurs naturally (less than 145 ppm). While effects of DDW on cancer started to be intensively studied, the effects on cardiovascular system are completely unknown. Thus, we aimed to analyze the effects of DDW (55+/-5 ppm) administration to 12-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) treated with 15 % fructose for 6 weeks. Blood pressure (BP) and selected biochemical parameters were measured together with determination of nitric oxide synthase (NOS) activity and iNOS and eNOS protein expressions in the left ventricle (LV) and aorta...
October 24, 2016: Physiological Research
J Klimentova, M Cebova, A Barta, Z Matuskova, S Vrankova, R Rehakova, M Kovacsova, O Pechanova
Melatonin, a multitasking indolamine, seems to be involved in a variety of physiological and metabolic processes via both receptor-mediated and receptor-independent mechanisms. The aim of our study was to find out whether melatonin can affect blood pressure (BP), nitric oxide synthase (NOS) activity, eNOS and nNOS protein expressions in rats with metabolic syndrome (SHR/cp). Rats were divided into four groups: 6-week-old male WKY andSHR/cp and age-matched WKY and SHR/cp treated with melatonin (10 mg/kg/day) for 3 weeks...
October 24, 2016: Physiological Research
Miao Liu, Xing Xing Liu, Xiao Lin He, Li Juan Liu, Hao Wu, Cai Xian Tang, Yong Song Zhang, Chong Wei Jin
Nitric oxide (NO) and ethylene respond to biotic and abiotic stresses through either similar or independent processes. This study examines the mechanism underlying the effects of NO and ethylene on promoting root hair development in Arabidopsis under magnesium (Mg) deficiency. The interaction between NO and ethylene in the regulation of Mg deficiency-induced root hair development was investigated using NO- and ethylene-related mutants and pharmacological methods. Mg deficiency triggered a burst of NO and ethylene, accompanied by a stimulated development of root hairs...
October 24, 2016: New Phytologist
Sana Iqbal, Erik G Hayman, Caron Hong, Jesse A Stokum, David B Kurland, Volodymyr Gerzanich, J Marc Simard
Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH...
2016: Brain Circulation
Vitor Castania, Ana Carolina Issy, João Walter Silveira, Frederico Rogério Ferreira, Simoneide S Titze-de-Almeida, Fernando F B Resende, Nádia Rubia Ferreira, Ricardo Titze-de-Almeida, Helton L A Defino, Elaine Del Bel
Intervertebral disk degeneration is a progressive and debilitating disease with multifactorial causes. Nitric oxide (NO) might contribute to the cell death pathway. We evaluated the presence of the constitutive form of the neuronal NOS (nNOS) in both health and degenerated intervertebral disk through qPCR and immunohistochemistry. We also analyzed the potential role of nNOS modulation in the tail needle puncture model of intervertebral disk degeneration. Male Wistar rats were submitted to percutaneous disk puncture with a 21-gauge needle of coccygeal vertebras...
October 19, 2016: Neurotoxicity Research
Francisco Molina, María Luisa Del Moral, María Ángeles Peinado, Alma Rus
BACKGROUND: Nitric oxide (NO) appears to play a key role in the hypoxic injury to the brain. We have previously reported that hypoxia/reoxygenation downregulated NO synthases (NOS) in the adult striatum. Until now, no data were available concerning the influence of aging in conjunction with hypoxia/reoxygenation on the NO system in the striatum. OBJECTIVE: The aim of this study was to assess the role of the NO pathway in the hypoxic aged striatum. METHODS: Wistar rats 24-25 months old were submitted to hypobaric hypoxia (20 min)/reoxygenation (0 h, 24 h, 5 days)...
October 20, 2016: Gerontology
Somasundaram Ramasamy, Mohammad Mahfuzul Haque, Mahinda Gangoda, Dennis J Stuehr
The NO synthases (NOS) catalyze a two-step oxidation of L-Arginine (Arg) to generate NO. In the first step, O2 activation involves one electron being provided to the heme by an enzyme-bound 6R-tetrahydro-L-biopterin cofactor (H4 B), which then forms a H4 B radical that must be reduced back to H4 B in order for NOS to continue catalysis. Although an NADPH-derived electron is used to reduce the H4 B radical, how this occurs is unknown. We hypothesized that the NOS flavoprotein domain might reduce the H4 B radical by utilizing the NOS heme porphyrin as a conduit to deliver the electron...
October 19, 2016: FEBS Journal
Shu-Jian Wei, Lin Cheng, Er-Shun Liang, Qi Wang, Sheng-Nan Zhou, Hao Xu, Long-Hua Hui, Zhi-Ming Ge, Ming-Xiang Zhang
Poly (ADP-ribose) polymerase (PARP) plays an important role in endothelial dysfunction, leading to atherogenesis and vascular-related diseases. However, whether PARP regulates nitric oxide (NO), a key regulator of endothelial function, is unclear so far. We investigated whether inhibition of PARP-1, the most abundant PARP isoform, prevents atherogenesis by regulating NO production and tried to elucidate the possible mechanisms involved in this phenomenon. In apolipoprotein E-deficient (apoE(-/-) ) mice fed a high-cholesterol diet for 12 weeks, PARP-1 inhibition via treatment with 3,4-dihydro-54-(1-piperindinyl) butoxy-1(2H)-isoquinoline (DPQ) or PARP-1 gene knockoutreduced aortic atherosclerotic plaque areas (49% and 46%, respectively)...
October 18, 2016: Clinical and Experimental Pharmacology & Physiology
Tijen Kaya Temiz, Omer Demir, Fatma Simsek, Yusuf Cem Kaplan, Selen Bahceci, Barıs Karadas, Aslı Celik, Gokhan Koyluoglu
AIM: The aim of this study is to investigate whether nitric oxide (NO)-mediated colonic motility was altered in rat irritable bowel syndrome (IBS) model, using different isoforms of NO-synthase (NOS) inhibitors. MATERIALS AND METHODS: The animal model of IBS-like visceral hypersensitivity was induced by intra-colonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8 to 21. Control animals received saline instead of AA. Experiments were performed at the end of 8 weeks...
July 2016: Indian Journal of Pharmacology
Hugo Huisman, Aletta Schutte, Johannes Van Rooyen, Carla Fourie, Ruan Kruger, Wayne Smith, Leandi Lammertyn, Leone Malan, Shani Botha, Carina Mels
OBJECTIVE: Tetrahydrobiopterin (BH4) is a cofactor for nitric oxide synthase (NOS) and may be a critical agent in endothelial function by improving nitric oxide (NO) mediated effects. It is reported that the NO synthesis capacity seems favourable in blacks despite their adverse cardiovascular profile. We therefore compared the concentrations of BH4, as well as blood pressure (BP) and arterial stiffness between black and white teachers. Furthermore, we tested the associations of BH4 with a product and inhibitor of NO synthesis, namely L-citrulline, and symmetric dimethylarginine (SDMA) respectively, in both ethnic groups...
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
Qiongying Wang, Jeong Euy-Myoung, Hong Liu, Lianzhi Gu, Samuel C Dudley, Jing Yu
OBJECTIVE: The saponin Astragaloside IV (ASI) reportedly enhances endothelial NOS (eNOS) activity by increasing the scavenging of reactive oxygen species (ROS) and NO production. We hypothesized that oxidative stress may decrease eNOS phosphorylation and result in diastolic dysfunction in DOCA-salt mice, which could be reversed by ASI treatment. DESIGN AND METHOD: We used the deoxycorticosterone acetate (DOCA)-salt mouse model. The mice were divided into four groups; SHAM and DOCA control mice received sterile water, SHAM+ASI and DOCA+ASI received ASI treatment via an intraperitoneal injection of 0...
September 2016: Journal of Hypertension
Jasjeet Bhullar, Veena M Bhopale, Ming Yang, Kinjal Sethuraman, Stephen R Thom
This investigation explored the mechanism for microparticles (MPs) production by human and murine platelets exposed to high pressures of inert gases. Results demonstrate that MPs production occurs via an oxidative stress response in a dose-dependent manner and follows the potency series N2 > Ar > He. Gases with higher van der Waals volumes or polarizability such as SF6 and N2O, or hydrostatic pressure, do not cause MPs production. Singlet O2 is generated by N2, Ar and He, which is linked to NADPH oxidase (NOX) activity...
October 14, 2016: Free Radical Biology & Medicine
Juneo F Silva, Natália M Ocarino, Rogéria Serakides
The gene and/or protein expression of proteases and immunological, angiogenic, hormonal and apoptotic mediators was evaluated in rat placenta before and during intrauterine trophoblast migration. The depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk1), interferon (IFN)-γ, migration inhibitory factor (MIF), and inducible nitric oxide synthase (iNOS; also known as nitric oxide synthase (NOS) 2) were evaluated...
October 14, 2016: Reproduction, Fertility, and Development
Naoto Fujii, Sheila M Dervis, Ronald J Sigal, Glen P Kenny
Both cyclooxygenase (COX) and nitric oxide synthase (NOS) contribute to sweating, whereas NOS alone contributes to cutaneous vasodilation during exercise in the heat. Here, we evaluated if type 1 diabetes mellitus (T1DM) modulates these responses. Adults with (n=11, 25±5 years) and without (n=12, 24±4 years) T1DM performed two bouts of 30-min cycling at a fixed rate of heat production of 400W in the heat (35°C); each followed by a 20- and 40-min recovery period respectively. Sweat rate and cutaneous vascular conductance (CVC) were measured at four intradermal microdialysis sites treated with either 1) lactated Ringer (vehicle control site), 2) 10mM ketorolac (non-selective COX inhibitor), 3) 10mM N(G)-nitro-L-arginine methyl ester (non-selective NOS inhibitor), or 4) a combination of both inhibitors...
October 12, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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