title: Hypoxia stimulates release of ANP and BNP from perfused rat ventricular myocardium.
abstract: We determined the effect of hypoxia on cellular energy state and ventricular atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and endothelin-1 (ET-1) release in an isolated perfused heart preparation after removal of all atrial tissue in 21- to 24-mo-old Wistar-Kyoto rats. After a control period (14 min), the ventricles (n = 6) were exposed to 30 min of hypoxia by changing the gas mixture to N2-CO2 (95:5 vol/vol; hypoxic period) and back to O2-CO2 (95:5 vol/vol) for 30 min (reoxygenation period). Control hearts (n = 6) were perfused throughout the experiment (74 min) with oxygenated Krebs-Henseleit phosphate-free buffer. In parallel experiments, the metabolic state of oxygenated (n = 4) and hypoxic (n = 5) ventricles was assessed using 31P-nuclear magnetic resonance (31P-NMR). Hypoxia caused a rapid decrease in left ventricular peak systolic pressure associated with a 2.1-fold increase (27.6 +/- 2.2 to 58.0 +/- 13.1 fmol/ml; P < 0.05) in the concentration of immunoreactive (ir) ANP and a 1.6-fold increase (2.5 +/- 0.2 to 3.9 +/- 0.5 fmol/ml; P < 0.05) in the [irBNP] (where brackets signify concentration) in the perfusate. In contrast, perfusate [irET-1] (1.2 +/- 0.2 fmol/ml) did not change significantly during hypoxia. 31P-NMR showed that the [ATP]-to-[ADP].[Pi] ratio was reduced during hypoxia with a simultaneous increase in intracellular monophosphates and perfusate [irANP] and [irBNP]. The decrease in the cytosolic pH during hypoxia was small. High-performance liquid chromatography of the perfusates showed that the ANP-like immunoreactive material released corresponded to the processed, low-molecular weight peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University of Oulu, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Tóth
authors.forename: K H
authors.initials: KH
authors.lastname: Vuorinen
authors.forename: O
authors.initials: O
authors.lastname: Vuolteenaho
authors.forename: I E
authors.initials: IE
authors.lastname: Hassinen
authors.forename: P A
authors.initials: PA
authors.lastname: Uusimaa
authors.forename: J
authors.initials: J
authors.lastname: Leppäluoto
authors.forename: H
authors.initials: H
authors.lastname: Ruskoaho
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000737:chemistry / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism; D004734:Energy Metabolism; D006352:Heart Ventricles; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D011312:Pressure; D051381:Rats; D011921:Rats, Inbred WKY; D013599:Systole
chemical_list: D016232:Endothelins; D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D007770:L-Lactate Dehydrogenase; D010100:Oxygen