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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wong, P. S. Garle, M. J. Alexander, S. P. H. Randall, M. D. Roberts, R. E. |
| Description | Country affiliation: United kingdom Author Affiliation: Wong PS ( Pharmacology Research Group, School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.); Garle MJ ( Pharmacology Research Group, School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.); Alexander SP ( Pharmacology Research Group, School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.); Randall MD ( Pharmacology Research Group, School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. Electronic address: michael.randall@nottingham.ac.uk.); Roberts RE ( Pharmacology Research Group, School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.) |
| Abstract | Hydrogen peroxide (H2O2) has been proposed to act as a factor for endothelium-derived hyperpolarization (EDH) and EDH may act as a 'back up' system to compensate the loss of the NO pathway. Here, the mechanism of action of H2O2 in porcine isolated coronary arteries (PCAs) was investigated. Distal PCAs were mounted in a wire myograph and pre-contracted with U46619 (1nM-50µM), a thromboxane A2-mimetic or KCl (60mM). Concentration-response curves to H2O2(1µM-1mM), bradykinin (0.01nM-1µM), sodium nitroprusside (SNP) (10nM-10µM), verapamil (1nM-10µM), KCl (0-20mM) or Ca(2+)-reintroduction (1µM-10mM) were constructed in the presence of various inhibitors. Activity of the Na(+)/K(+)-pump was measured through rubidium-uptake using atomic absorption spectrophotometry. H2O2 caused concentration-dependent vasorelaxations with a maximum relaxation (Rmax) of 100±16% (mean±SEM), pEC50=4.18±0.20 (n=4) which were significantly inhibited by PEG-catalase at 0.1-1.0mM H2O2 (P<0.05). 10mM TEA significantly inhibited the relaxation up to 100µM H2O2 (P<0.05). 60mM K(+) and 500nM ouabain significantly inhibited H2O2-induced vasorelaxation producing a relaxation of 40.8±8.5% (n=5) and 47.5±8.6% (n=6) respectively at 1mM H2O2 (P<0.0001). H2O2-induced vasorelaxation was unaffected by the removal of endothelium, inhibition of NO, cyclo-oxygenase, gap junctions, SKCa, IKCa, BKCa Kir, KV, KATP or cGMP. 100µM H2O2 had no effects on the KCl-induced vasorelaxation or Ca(2+)-reintroduction contraction. 1mM H2O2 inhibited both KCl-induced vasorelaxation and rubidium-uptake consistent with inhibition of the Na(+)/K(+)-pump activity. We have shown that the vascular actions of H2O2 are sensitive to ouabain and high concentrations of H2O2 are able to modulate the Na(+)/K(+)-pump. This may contribute towards its vascular actions. |
| File Format | HTM / HTML |
| ISSN | 10436618 |
| Volume Number | 90 |
| e-ISSN | 10961186 |
| Journal | Pharmacological Research |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2014-12-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Pharmacology Coronary Vessels Physiology Hydrogen Peroxide Pharmacology Sodium-potassium-exchanging Atpase Vasodilation Drug Effects Animals Bradykinin Carbenoxolone Catalase Colforsin Female In Vitro Techniques Indomethacin Male Ng-nitroarginine Methyl Ester Nitroprusside Ouabain Oxadiazoles Peptides Polyethylene Glycols Quinoxalines Antagonists & Inhibitors Swine Vasoconstrictor Agents Verapamil Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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