Role of myocardial redox and energy states in ischemia-stimulated release of atrial natriuretic peptide.
The correlations between myocardial redox and energy states and atrial natriuretic peptide (ANP) secretion were studied in the perfused rat heart by exposing the hearts to global and low-flow ischemia for varying periods. Atrial and ventricular energy states and immunoreactive ANP in the effluent perfusate were measured. The basal secretion rate of ANP was 2.7 +/- 0.2 ng/min.g dry wt and it was stimulated 2.6 +/- 0.4, 4.0 +/- 0.6, 11.2 +/- 2.1 and 13.3 +/- 3.2-fold (means +/- S.E.) at the time point of 2 min after 5, 10, 20 and 30-min periods of ischemia, respectively. The increase in ANP release during the post-ischemic period was statistically significant and showed positive linear correlation with the atrial and ventricular lactate/pyruvate ratios (r = 0.92 and 0.89, respectively) and negative non-linear correlation with the atrial and ventricular phosphorylation potentials (r = -0.97 and -0.94, respectively). In agreement with the enhanced release of ANP after global ischemia, low-flow ischemia also increased ANP release. Cellular damage was not evidently responsible for the increased secretion, because only ANP1-28, the processed form of the peptide, was detected in the perfusates and no processing of exogenous proANP during or after ischemia was observed. These results indicate that myocardial ischemia stimulates ANP release and suggest that cellular redox and energy states may be linked to ANP release during ischemia/reperfusion. Thus, ANP release during and after ischemia in vivo may be due not only to atrial distention but also to changes in energy metabolism.
Uusimaa
P A
PA
Department of Medical Biochemistry, University of Oulu, Finland.
Peuhkurinen
K J
KJ
Vuolteenaho
O
O
Ruskoaho
H
H
Hassinen
I E
IE
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D009320:Atrial Natriuretic Factor