Acute myocardial hypoxia increases BNP gene expression.
It is well established that cardiac failure increases cardiac B-type natriuretic peptide (BNP) expression due to myocardial stretching. However, patients with ischemic heart disease also display increased plasma BNP and proBNP concentrations despite preserved cardiac function. In this study, we examined whether acute myocardial hypoxia increases cardiac BNP expression. Surgical reduction of the blood flow to an area of the anterior ventricular wall in pigs reduced the myocardial oxygen tension from 46 +/- 4 to 13 +/- 5 mmHg. The tissue contents of VEGF and BNP mRNA increased 1.8-fold and 3.5-fold, respectively (n=10, P<0.005) in hypoxic compared with normoxic ventricular myocardium after 2.2 +/- 0.2 h; the magnitude of the increase in BNP mRNA expression was positively correlated with that of VEGF in hypoxic myocardium (r=0.66, P<0.05). In support of a hypoxia-induced increase of BNP gene transcription, the content of a premature BNP mRNA was increased in hypoxic myocardium (4.8-fold, P<0.005) and in freshly harvested ventricular myocytes when kept in culture flasks and oxygen-deprived for 3 h (2.2-fold, P=0.002). ProBNP peptide accumulated in the medium of freshly harvested ventricular myocyte cultures but was undetectable in ventricular myocardium, indicating rapid release of the newly synthesized proBNP peptide. Accordingly, the plasma proBNP concentration increased after 2 h of myocardial hypoxia (P=0.028). Cumulatively, the data suggest that acute hypoxia stimulates cardiac BNP expression.
Goetze
J P
JP
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Gore
A
A
Møller
C H
CH
Steinbrüchel
D A
DA
Rehfeld
J F
JF
Nielsen
L B
LB
D000818:Animals; D015687:Cell Hypoxia; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013552:Swine
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain