title: Oxidative stress augments the secretion of atrial natriuretic peptide in isolated rat atria.
abstract: Reactive oxygen species (ROS) play a role in cardiovascular diseases such as hypertension and heart failure. The objective of the present study was to investigate the role of endogenous ROS in atrial hemodynamics and ANP secretion in isolated perfused beating rat atria. Pyrogallol (a generator of superoxide anion, 0.1, 1mM) or hydrogen peroxide (0.1, 1, 10, 30mM) was perfused into atria paced at 1.2Hz. Pyrogallol and hydrogen peroxide stimulated ANP secretion and concentration in a dose-dependent manner and dramatically decreased atrial contractility and translocation of extracellular fluid. The stimulatory effect of pyrogallol and hydrogen peroxide on ANP secretion was attenuated by the pretreatment with ascorbic acid (an antioxidant; 1mM) and cariporide (an inhibitor of the Na(+)/H(+) exchanger; 1μM) but negative inotropic effect was not changed. U120 (a MAPK(erk) pathway inhibitor; 10μM) attenuated the stimulatory effect of hydrogen peroxide on ANP secretion. However, U120 augmented negative inotropic effect and stimulatory effect of ANP concentration induced by pyrogallol. Antioxidant such as N-acetyl cystein, gallate, propyl gallate, or ellagic acid did not cause any significant changes in atrial parameters. These results suggest that intracellular - formed ROS stimulates ANP secretion partly through activation of MAPK(erk) pathway and Na(+)/H(+) exchanger.
authors: Department of Physiology, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors: Amin
authors: A
authors: Shah
authors: Shan
authors: S
authors: Gao
authors: Young-Bin
authors: YB
authors: Oh
authors: Woo Hyun
authors: WH
authors: Park
authors: Suhn Hee
authors: SH
authors: Kim
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000503:physiopathology; D045604:Extracellular Fluid / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000009:adverse effects; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects*; D011435:Propyl Gallate / Q000494:pharmacology; D011748:Pyrogallol / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D013450:Sulfones / Q000494:pharmacology
chemical_list: D006146:Guanidines; D017382:Reactive Oxygen Species; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D011748:Pyrogallol; C093373:cariporide; D009320:Atrial Natriuretic Factor; D011435:Propyl Gallate; D006861:Hydrogen Peroxide; D020929:Mitogen-Activated Protein Kinase Kinases; D001205:Ascorbic Acid; D000111:Acetylcysteine