Hypoxia stimulates release of ANP and BNP from perfused rat ventricular myocardium.
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)
Tóth
M
M
Department of Pharmacology, University of Oulu, Finland.
Vuorinen
K H
KH
Vuolteenaho
O
O
Hassinen
I E
IE
Uusimaa
P A
PA
Leppäluoto
J
J
Ruskoaho
H
H
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
D016232:Endothelins; D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D007770:L-Lactate Dehydrogenase; D010100:Oxygen