NPPB and ischemia: When cardiomyocytes are subjected to a stimulus such as mechanical stress, pressure or volume overload, certain hormones (e.g., angiotensin II or endothelin), cytokines, or ischemia, BNP gene expression is transcriptionally upregulated through actions of the aforementioned transcription factors [44,45,46], and the resulting transcript is translated in the endoplasmic reticulum to produce preproBNP [26,27].