title: Improved cardiac contractile functions in hypoxia-reoxygenation in rats treated with low concentration Co(2+).
abstract: An intracellular mechanism that senses decreases in tissue oxygen level and stimulates hypoxia-related gene expression has been reported in various cell types including the cardiac cell. The mechanism can also be activated by Co(2+) in normoxia. Thus we investigated the effects of prior chronic oral CoCl(2) on mechanical functions of isolated, perfused rat hearts in hypoxia-reoxygenation. In normoxic rats, 43 days of Co(2+) administration increased hematocrit from 45 +/- 0.3% (control, n = 18) to 51 +/- 0.6% (n = 19). In hypoxia and reoxygenation, Co(2+)-pretreated hearts exhibited a significantly higher rate-pressure product (267 and 163%, respectively) and coronary flow (127 and 118%, respectively) and lower end-diastolic pressure (72 and 60%, respectively) compared with the control hearts. Although the oral Co(2+) administration significantly raised myocardial Co(2+) concentration, it did not affect mitochondrial respiration, tissue glycogen concentration, or myocardial tissue histology. The levels of vascular endothelial growth factor, aldolase-A, and glucose transporter-1 mRNA were significantly elevated in the Co(2+)-treated myocardium. We conclude that cardiac contractile functions would gain hypoxic tolerance when the endogenous cellular oxygen-sensing mechanism is activated.
authors.affiliation: Department of Physiology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Endoh
authors.forename: T
authors.initials: T
authors.lastname: Kaneko
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Doi
authors.forename: E
authors.initials: E
authors.lastname: Takahashi
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology; D006400:Hematocrit; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D016587:Antimutagenic Agents; D003035:Cobalt; D006003:Glycogen; C018021:cobaltous chloride