title: Suppression of high pacing-induced ANP secretion by antioxidants in isolated rat atria.
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. H(2)O(2) 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.
authors: 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.
authors: Shan
authors: S
authors: Gao
authors: Kuichang
authors: K
authors: Yuan
authors: Amin
authors: A
authors: Shah
authors: Jong Suk
authors: JS
authors: Kim
authors: Woo Hyun
authors: WH
authors: Park
authors: Suhn Hee
authors: SH
authors: Kim
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016275:Atrial Function / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure; D002304:Cardiac Pacing, Artificial; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004558:Electric Stimulation; D004789:Enzyme Activation; D045604:Extracellular Fluid / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D006439:Hemodynamics; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011748:Pyrogallol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013113:Spin Labels; D008063:Thioctic Acid / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D011748:Pyrogallol; D008063:Thioctic Acid; D009320:Atrial Natriuretic Factor; C056165:acetovanillone; D006861:Hydrogen Peroxide; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C001803:tempol; D000111:Acetylcysteine