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Vasorelaxation

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https://www.readbyqxmd.com/read/28924052/role-of-the-endothelial-caveolae-microdomain-in-shear-stress-mediated-coronary-vasorelaxation
#1
Tong Lu, Xiao-Li Wang, Qiang Chai, Xiaojing Sun, Gary C Sieck, Zvonimir S Katusic, Hon-Chi Lee
In this study, we determined the role of caveolae and the ionic mechanisms that mediate shear stress-mediated vasodilation (SSD). We found that both TRPV4 and SK channels are targeted to caveolae in freshly isolated bovine coronary endothelial cells (BCECs) and that TRPV4 and KCa2.3 (SK3) channels are co-immunoprecipitated by anti-caveolin-1 antibodies. Acute exposure of BCECs seeded in a capillary tube to 10 dynes/cm2 of SS resulted in activation of TRPV4 and SK currents. However, after incubation with HC067047 (TRPV4 inhibitor) SK currents could no longer be activated by SS, suggesting SK channel activation by SS was mediated through TRPV4...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28912066/the-camp-effectors-pka-and-epac-activate-endothelial-no-synthase-through-pi3k-akt-pathway-in-human-endothelial-cells
#2
Verónica García-Morales, María Luaces-Regueira, Manuel Campos-Toimil
3',5'-cyclic adenosine monophosphate (cAMP) exerts an endothelium-dependent vasorelaxant action by stimulating endothelial NO synthase (eNOS) activity, and the subsequent NO release, through cAMP protein kinase (PKA) and exchange protein directly activated by cAMP (Epac) activation in endothelial cells. We have here investigated the mechanism by which the cAMP-Epac/PKA pathway activates eNOS. cAMP-elevating agents (forskolin and dibutyryl-cAMP) and the joint activation of PKA (6-Bnz-cAMP) and Epac (8-pCPT-2'-O-Me-cAMP) increased cytoplasmic Ca(2+) concentration ([Ca(2+)]c) in ≤ 30% of fura-2-loaded isolated human umbilical vein endothelial cells (HUVEC)...
September 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28894214/the-novel-compound-sul-121-preserves-endothelial-function-and-inhibits-progression-of-kidney-damage-in-type-2-diabetes-mellitus-in-mice
#3
S P H Lambooy, A Bidadkosh, D Nakladal, A van Buiten, R A T Girgis, A C van der Graaf, T J Wiedenmann, R A Koster, P Vogelaar, H Buikema, R H Henning, L E Deelman
Diabetic nephropathy is still a common complication of type 2 diabetes mellitus (T2DM) and improvement of endothelial dysfunction (ED) and inhibition of reactive oxygen species (ROS) are considered important targets for new therapies. Recently, we developed a new class of compounds (Sul compounds) which inhibit mitochondrial ROS production. Here, we tested the therapeutic effects of Sul-121 on ED and kidney damage in experimental T2DM. Diabetic db/db and lean mice were implanted with osmotic pumps delivering Sul-121 (2...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893911/molecular-and-functional-characterization-of-the-endothelial-atp-sensitive-potassium-channel
#4
Qadeer Aziz, Yiwen Li, Naomi Anderson, Leona Ojake, Elena Tsisanova, Andrew Tinker
ATP-sensitive potassium (KATP) channels are widely expressed in the cardiovascular system where they regulate a range of biological activities by linking cellular metabolism with membrane excitability. KATP channels in vascular smooth muscle have a well-defined role in regulating vascular tone. KATP channels are also thought to be expressed in vascular endothelial cells (ECs), but their presence and function in this context is less clear. As a result, we aimed to investigate the molecular composition and physiological role of endothelial KATP channels...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28887333/rapid-estrogen-receptor-alpha-signaling-mediated-by-erk-activation-regulates-vascular-tone-in-male-and-ovary-intact-female-mice
#5
Seong Chul Kim, Austin C Boese, Matthew H Moore, Rea M Cleland, Lin Chang, Patrice Delafontaine, Ke-Jie Yin, Jean-Pyo Lee, Milton H Hamblin
Estrogen has been shown to affect vascular reactivity. Here, we assessed estrogen receptor-alpha (ERα) dependency of estrogenic effects on vasorelaxation via a rapid nongenomic pathway in both male and ovary-intact female mice. We compared the effect of a primary estrogen, 17 beta-estradiol (E2) or 4,4',4"-(4-propyl-[1H]pyrazole-1,3,5-triyl)tris-phenol (PPT) (selective ERα agonist). We found that E2 and PPT induced greater aortic relaxation in females than males, indicating ERα mediation, which is further validated by employing ERα antagonism...
September 8, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28882814/opsin-3-and-4-mediate-light-induced-pulmonary-vasorelaxation-that-is-potentiated-by-g-protein-receptor-kinase-2-inhibition
#6
Sebastian Barreto Ortiz, Daijiro Hori, Yohei Nomura, Xin Yun, Haiyang Jiang, Hwanmee Yong, James Chen, Sam Paek, Deepesh Pandey, Gautam Sikka, Anil Bhatta, Andrew Gillard, Jochen Steppan, Jae Hyung Kim, Hideo Adachi, Viachaslau Barodka, Lewis Romer, Steven S An, Larissa A Shimoda, Lakshmi Santhanam, Dan E Berkowitz
We recently demonstrated that blue light induces vasorelaxation in the systemic mouse circulation, a phenomenon mediated by the non-visual G protein-coupled receptor (GPCR) melanopsin (opsin 4; Opn4). Here we tested the hypothesis that non-visual opsins mediate photorelaxation in the pulmonary circulation. We discovered Opsin 3 (Opn3), Opn4, and G-protein coupled receptor kinase 2 (GRK2) in rat pulmonary arteries (PAs) and in pulmonary arterial smooth muscle cells (PASMCs), where the opsins interact directly with GRK2 as demonstrated with a proximity ligation assay...
September 7, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28881660/activation-of-perk-branch-of-er-stress-mediates-homocysteine-induced-bkca-channel-dysfunction-in-coronary-artery-via-foxo3a-dependent-regulation-of-atrogin-1
#7
Wen-Tao Sun, Xiang-Chong Wang, Shiu-Kwong Mak, Guo-Wei He, Xiao-Cheng Liu, Malcolm John Underwood, Qin Yang
The molecular mechanism of endoplasmic reticulum (ER) stress in vascular pathophysiology remains inadequately understood. We studied the role of ER stress in homocysteine-induced impairment of coronary dilator function, with uncovering the molecular basis of the effect of ER stress on smooth muscle large-conductance Ca(2+)-activated K(+) (BKCa) channels. The vasodilatory function of BKCa channels was studied in a myograph using endothelium-denuded porcine small coronary arteries. Primary cultured porcine coronary artery smooth muscle cells were used for mRNA and protein measurements and current recording of BKCa channels...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28870455/pharmacological-evaluation-of-metformin-and-n-benzylbiguanide-a-novel-analogue-of-metformin-on-the-vasopressor-responses-to-adrenergic-system-stimulation-in-pithed-rats-with-fructose-induced-insulin-resistance
#8
Erika J Gutiérrez-Lara, Gabriel Navarrete-Vázquez, Araceli Sánchez-López, David Centurión
Metformin has been associated with cardioprotection, vasorelaxation and normalization of endothelial function during type 2 Diabetes Mellitus. However, few studies have analysed its effects on vascular adrenergic system. Our study has evaluated the vasopressor responses induced by sympathetic stimulation or by i.v. bolus injections of the agonists noradrenaline (α1/2), methoxamine (α1) and UK 14,304 (α2) in rats with fructose-induced insulin resistance chronically pretreated with either metformin or EGL-6M (N-benzylbiguanide), a novel analogue of metformin...
September 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28867591/heteromeric-trpv4-trpc1-channels-mediate-calcium-sensing-receptor-induced-nitric-oxide-production-and-vasorelaxation-in-rabbit-mesenteric-arteries
#9
Harry Z E Greenberg, Simonette R E Carlton-Carew, Dhanak M Khan, Alexander K Zargaran, Kazi S Jahan, W-S Vanessa Ho, Anthony P Albert
Stimulation of calcium-sensing receptors (CaSR) by increasing the external calcium concentration (Ca(2+)]o) induces endothelium-dependent vasorelaxation through nitric oxide (NO) production and activation of intermediate Ca(2+)-activated K(+) currents (IKCa) channels in rabbit mesenteric arteries. The present study investigates the potential role of heteromeric TRPV4-TRPC1 channels in mediating these CaSR-induced vascular responses. Immunocytochemical and proximity ligation assays showed that TRPV4 and TRPC1 proteins were expressed and co-localised at the plasma membrane of freshly isolated endothelial cells (ECs)...
September 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28856926/total-flavonoids-from-astragalus-alleviate-endothelial-dysfunction-by-activating-the-akt-enos-pathway
#10
Qian Liu, Ling Zhang, Qiyuan Shan, Yuxia Ding, Zhaocai Zhang, Meifei Zhu, Yuanjie Mao
Objective To investigate the vasodilative and endothelial-protective effects and the underlying mechanisms of total flavonoids from Astragalus (TFA). Methods The vasodilative activities of TFA were measured with a myograph ex vivo using rat superior mesenteric arterial rings. The primary human umbilical vein endothelial cell (HUVEC) viabilities were assayed using the cell counting kit-8 after hypoxia or normoxia treatment with or without TFA. Akt, P-Akt, eNOS, P-eNOS, Erk, P-Erk, Bcl-2 and Bax expression were analyzed using western blotting...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28855531/oxidant-sensor-in-the-cgmp-binding-pocket-of-pkgi%C3%AE-regulates-nitroxyl-mediated-kinase-activity
#11
Sonia Donzelli, Mara Goetz, Kjestine Schmidt, Markus Wolters, Konstantina Stathopoulou, Simon Diering, Oleksandra Prysyazhna, Volkan Polat, Jenna Scotcher, Christian Dees, Hariharan Subramanian, Elke Butt, Alisa Kamynina, Sophie Schobesberger, S Bruce King, Viacheslav O Nikolaev, Cor de Wit, Lars I Leichert, Robert Feil, Philip Eaton, Friederike Cuello
Despite the mechanisms for endogenous nitroxyl (HNO) production and action being incompletely understood, pharmacological donors show broad therapeutic promise and are in clinical trials. Mass spectrometry and site-directed mutagenesis showed that chemically distinct HNO donors 1-nitrosocyclohexyl acetate or Angeli's salt induced disulfides within cGMP-dependent protein kinase I-alpha (PKGIα), an interdisulfide between Cys42 of the two identical subunits of the kinase and a previously unobserved intradisulfide between Cys117 and Cys195 in the high affinity cGMP-binding site...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855109/the-vasorelaxant-effect-of-mitiglinide-via-activation-of-voltage-dependent-k-channels-and-serca-pump-in-aortic-smooth-muscle
#12
Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L Firth, Il-Whan Choi, Il Yong Han, Dae-Sung Lee, Mi-Jin Yim, Won Sun Park
AIMS: The vasorelaxant effects of the anti-diabetic drug, mitiglinide in phenylephrine (Phe)-pre-contracted aortic rings were examined. MATERIALS AND METHODS: Arterial tone measurement was performed in aortic smooth muscle cells. KEY FINDINGS: Mitiglinide dose-dependently induced vasorelaxation. Application of the large-conductance Ca(2+)-activated K(+) (BKCa) channel blocker paxilline, inwardly rectifying K(+) (Kir) channel blocker Ba(2+), and ATP-sensitive K(+) (KATP) channel blocker glibenclamide did not affect the vasorelaxant effect of mitiglinide...
August 27, 2017: Life Sciences
https://www.readbyqxmd.com/read/28852218/a-rare-genetic-variant-of-bpifb4-predisposes-to-high-blood-pressure-via-impairment-of-nitric-oxide-signaling
#13
Carmine Vecchione, Francesco Villa, Albino Carrizzo, Chiara Carmela Spinelli, Antonio Damato, Mariateresa Ambrosio, Anna Ferrario, Michele Madonna, Annachiara Uccellatore, Silvia Lupini, Anna Maciag, Larisa Ryskalin, Luciano Milanesi, Giacomo Frati, Sebastiano Sciarretta, Riccardo Bellazzi, Stefano Genovese, Antonio Ceriello, Alberto Auricchio, Alberto Malovini, Annibale Alessandro Puca
BPIFB4 is associated with exceptional longevity: four single-nucleotide polymorphisms distinguish the wild-type form from a longevity-associated variant conferring positive effects on blood pressure. The effect of a rare variant (RV; allele frequency, 4%) on blood pressure is unknown. Here, we show that overexpression of RV-BPIFB4 in ex-vivo mouse vessels impairs phosphorylation of endothelial nitric oxide synthase (eNOS), blunting acetylcholine-evoked vasorelaxation; in vivo, virally mediated overexpression of RV-BPIFB4 increases blood pressure, an action absent in eNOS-deficient mice...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28840751/gastrodin-causes-vasodilation-by-activating-katp-channels-in-vascular-smooth-muscles-via-pka-dependent-signaling-pathway
#14
Shuo Chen, Xuewei Hao, Lei Yu, Ping Zhang, Weiwei Cao, Hongyang Chen, Daling Zhu
Gastrodin, one of the major components extracted from the Chinese herb Gastrodia elata Bl., has been widely used as an anticonvulsant, sedative, analgesic and hypotensive. In our study, we aimed to investigate the effects and possible mechanisms of gastrodin on vascular KATP channels. Tension experiments were used on rat mesenteric artery rings without an endothelium. Patch clamp experiments were executed to investigate the influences of gastrodin on the membrane current in mesenteric artery smooth muscle cells...
August 25, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28839162/microrna-204-promotes-vascular-endoplasmic-reticulum-stress-and-endothelial-dysfunction-by-targeting-sirtuin1
#15
Modar Kassan, Ajit Vikram, Qiuxia Li, Young-Rae Kim, Santosh Kumar, Mohanad Gabani, Jing Liu, Julia S Jacobs, Kaikobad Irani
Endoplasmic reticulum (ER) stress has been implicated in vascular endothelial dysfunction of obesity, diabetes, and hypertension. MicroRNAs play an important role in regulating ER stress. Here we show that microRNA-204 (miR-204) promotes vascular ER stress and endothelial dysfunction by targeting the Sirtuin1 (Sirt1) lysine deacetylase. Pharmacologic ER stress induced by tunicamycin upregulates miR-204 and downregulates Sirt1 in the vascular wall/endothelium in vivo and in endothelial cells in vitro. Inhibition of miR-204 protects against tunicamycin-induced vascular/endothelial ER stress, associated impairment of endothelium-dependent vasorelaxation, and preserves endothelial Sirt1...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837342/cyperaceae-species-are-potential-sources-of-natural-mammalian-arginase-inhibitors-with-positive-effects-on-vascular-function
#16
Kamel Arraki, Perle Totoson, Alain Decendit, Alain Badoc, Andy Zedet, Julia Jolibois, Marc Pudlo, Céline Demougeot, Corine Girard-Thernier
The inhibition of arginase is of substantial interest for the treatment of various diseases of public health interest including cardiovascular diseases. Using an ex vivo experiment on rat aortic rings and an in vitro assay with liver bovine purified arginase, it was demonstrated that several polyphenolic extracts from Cyperus and Carex species possess vasorelaxant properties and mammalian arginase inhibitory capacities. Phytochemical studies performed on these species led to the identification of eight compounds, including monomers, dimers, trimers, and tetramers of resveratrol...
August 24, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28834298/the-vasorelaxant-effect-of-anti-diabetic-drug-nateglinide-via-activation-of-voltage-dependent-k-channels-in-aortic-smooth-muscle
#17
Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Won-Kyo Jung, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Hyoweon Bang, Il-Whan Choi, Sung Hun Na, Won Sun Park
AIMS: We investigated the vasorelaxant effect of nateglinide and its related mechanisms using phenylephrine (Phe)-induced pre-contracted aortic rings. METHODS: Arterial tone measurement was performed in aortic smooth muscle. RESULTS: The application of nateglinide induced vasorelaxation in a concentration-dependent manner. Pretreatment with the large conductance Ca(2+) -activated K(+) (BKCa ) channel inhibitor paxilline, the inwardly rectifying K(+) (Kir) channel inhibitor Ba(2+) , and ATP-sensitive K(+) (KATP ) channel inhibitor glibenclamide, did not affect the vasorelaxant effect of nateglinide...
August 20, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28832263/vasorelaxant-properties-of-vernonia-amygdalina-ethanol-extract-and-its-possible-mechanism
#18
Yung Sing Ch'ng, Yean Chun Loh, Chu Shan Tan, Mariam Ahmad, Mohd Zaini Asmawi, Wan Maznah Wan Omar, Mun Fei Yam
CONTEXT: Vernonia amygdalina Del. (VA) (Asteraceae) is commonly used to treat hypertension in Malaysia. OBJECTIVE: This study investigates the vasorelaxant mechanism of VA ethanol extract (VAE) and analyzes its tri-step FTIR spectroscopy fingerprint. MATERIALS AND METHODS: Dried VA leaves were extracted with ethanol through maceration and concentrated using rotary evaporator before freeze-dried. The vasorelaxant activity and the underlying mechanisms of VAE using the cumulative concentration (0...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28830209/puerarin-improves-vascular-insulin-resistance-and-cardiovascular-remodeling-in-salt-sensitive-hypertension
#19
Chunxiang Tan, Aimei Wang, Chan Liu, Yao Li, Yuepin Shi, Ming-Sheng Zhou
Puerarin is an isoflavonoid isolated from the Chinese herb, Kudzu roots (also known as Gegen), which has been widely used for the treatment of hypertensive diseases and diabetic mellitus in traditional Chinese medicine. Dahl salt-sensitive (DS) rat is a genetic model of salt-sensitive hypertension with cardiovascular injury and vascular insulin resistance. Here, we investigated whether puerarin improved vascular insulin resistance and attenuated cardiac and aortic remodeling in salt-sensitive hypertension. DS rats were given a normal (NS) or high salt diet (HS) for five weeks...
August 22, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28818791/low-density-lipoprotein-modified-by-myeloperoxidase-oxidants-induces-endothelial-dysfunction
#20
Adrian I Abdo, Benjamin S Rayner, David M van Reyk, Clare L Hawkins
Low-density lipoprotein (LDL) modified by hypochlorous acid (HOCl) produced by myeloperoxidase (MPO) is present in atherosclerotic lesions, where it is implicated in the propagation of inflammation and acceleration of lesion development by multiple pathways, including the induction of endothelial dysfunction. Thiocyanate (SCN(-)) ions are utilised by MPO to produce the oxidant hypothiocyanous acid (HOSCN), which reacts with LDL in a different manner to HOCl. Whilst the reactivity of HOCl-modified LDL has been previously studied, the role of HOSCN in the modification of LDL in vivo is poorly defined, although emerging evidence suggests that these particles have distinct biological properties...
August 5, 2017: Redox Biology
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