Atrial natriuretic hormone prohormone gene expression in cardiac and extra-cardiac tissues of diabetic Goto-Kakizaki rats.

The present investigation was designed to determine if the mechanism for the increased atrial natriuretic peptides within the circulation of diabetic animals involves atrial natriuretic hormone prohormone (proANH) gene expression upregulation. The tissue specificity of this potential upregulation of the proANH gene was investigated in a spontaneous model of type 2 diabetes, i.e. the Goto-Kakizaki (GK) rat with comparison to age-matched non-diabetic Wistar rats from which the GK colony was originally derived. Reverse transcription-polymerase chain reaction revealed that proANH gene expression was increased 3.1-fold in the left heart ventricle, 5-fold in lung, 2-fold in kidney, 3-fold within mucosa and 1.8-fold within muscle of gastric antrum (p < 0.05 for each) of GK rats compared to Wistar rats. There was no significant increase in proANH gene expression in atria and right ventricle of the heart of GK rats compared to Wistars. These results indicate that steady-state ANH prohormone mRNA levels increase within the left ventricle and extracardiac tissues in type 2 diabetic animals. This enhanced gene expression is a functional increase with its expressed proteins (4 peptide hormones; ANPs) increasing 2-6 fold within the circulation of GKs. The greater increase in proANH messenger RNA in the extracardiac tissues compared to the amount of increase within the heart and the greater tissue mass of these combined extra cardiac tissues suggests the majority of the increase in ANPs within the circulation of diabetics is secondary to increased synthesis in extracardiac tissues. This also suggests that there is a systemic regulatory mechanism of proANH gene expression not only within the heart but also within the lung, gastrointestinal tract and kidney. Diabetes is the first disease in which there is more upregulation of ANH prohormone in extracardiac tissues compared to upregulation within the heart itself.