Suppression of high pacing-induced ANP secretion by antioxidants in isolated rat atria |
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| Institution: | 1. Department of Physiology, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, 2-20 Keum-Am-Dong-San, Jeonju 561-180, Republic of Korea;2. Department of Biochemistry, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Republic of Korea;3. Department of Cardiology, Yanbian University Hospital, Yanji, Jilin Province, China;1. Department of Cellular Biology, 724 Biological Sciences Building, University of Georgia, Athens, Georgia 30602, USA;2. Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia 30602, USA;1. Department of Chemistry & Chemistry Research Center, Laboratories for Advanced Materials, United States Air Force Academy, Colorado Springs, Colorado, USA;2. Department of Chemistry, Clemson University, Clemson, South Carolina, USA;3. Department of Chemistry and Biochemistry, University of Colorado – Colorado Springs, Colorado Springs, Colorado, USA;1. Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, PR China;2. The 8th Brigade of General Division of Criminal Investigation, Beijing Municipal Public Security Bureau, Beijing 100006, PR China;1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, PO Box 1068, Blindern, 0316 Oslo, Norway;2. Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, PO Box 1068, Blindern, 0316 Oslo, Norway |
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| Abstract: | Reactive oxygen species (ROS) are formed as a natural by-product of the normal metabolism of oxygen and have important roles in cell signaling. The aim of this study was to investigate direct effects of ROS on atrial hemodynamics and ANP secretion in isolated perfused beating rat atria with antioxidants. When atria were paced at 1.2 Hz, N-acetyl cystein (antioxidant, NAC), α-lipoic acid (antioxidant), tempol (superoxide dismutase mimic), and apocynin (NADPH oxidase inhibitor; NOX inhibitor) did not affect ANP secretion and atrial contractility. When pacing frequency was increased from 1.2 Hz to 4 Hz, the ANP secretion increased and atrial contractility decreased. H2O2 level was increased in perfusate obtained from atria stimulated by high pacing frequency. NAC, α-lipoic acid and tempol attenuated high pacing frequency-induced ANP secretion but apocynin did not. In contrast, pyrogallol (a superoxide generator) augmented high pacing frequency-induced ANP secretion. NOX-4 protein was increased by high pacing stimulation and in diabetic rat atria. In diabetic rat atria, high pacing frequency caused an increased ANP secretion and a decreased atrial contractility, that were markedly attenuated as compared to control rats. NAC and apocynin reduced high pacing frequency-induced ANP secretion in diabetic rat atria. These results suggest that intracellular ROS formation partly through an increasing NOX activity in response to high pacing frequency is associated with an increased ANP secretion in rat atria. |
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