Suppression of B-type natriuretic peptide gene expression in cardiomyocytes under anoxic conditions

Abstract

Several cell biology studies have focused on the effects of hypoxic environments on cardiomyocytes. However, the effect of anoxic conditions on cardiomyocytes remains largely unexplored. In the present study, we investigated the direct effects of anoxia on B-type natriuretic peptide (BNP) gene expression in cardiomyocytes. Neonatal rat cardiomyocytes (NRCMs) were exposed to anoxia using an airtight chamber saturated with 95 % N₂/5 % CO₂. BNP mRNA levels in NRCM were substantially reduced after more than 8 h of anoxia exposure, whereas after reoxygenation, BNP gene expression levels recovered in a time-dependent manner and significantly increased after 24 h of reoxygenation. BNP mRNA levels suppressed under anoxic conditions were significantly increased by aldosterone-induced activation of sodium-proton exchanger 1 (NHE1), which was canceled by an NHE1 inhibitor, suggesting that anoxia reduces BNP gene expression, at least in part, in an NHE1-dependent manner. In summary, we found that BNP gene expression in cardiomyocytes decreases under anoxic conditions, in contrast to previous research findings that BNP expression increases under hypoxic conditions. These findings reveal a new insight that, within a single heart tissue in various cardiovascular diseases, such as myocardial infarction, the biological responses of cardiomyocytes are fundamentally different in regions of anoxia and hypoxia.