The infarction zone rather than the noninfarcted remodeling zone overexpresses angiotensin II receptor type 1 and is the main source of ventricular atrial natriuretic peptide.

Chromogranin B and inositol 1,4,5-trisphosphate-associated calcium signaling leading to increased natriuretic peptide production has been described in cardiac hypertrophy. Here, we performed left anterior descending coronary artery ligation in rats as a model for systolic heart failure and examined protein and gene expression clusters in the infarcted and noninfarcted myocardium and moreover under treatment with metoprolol. We found that atrial natriuretic peptide gene transcription was significantly more elevated in the infarcted compared with the noninfarcted myocardium. Chromogranin B, which facilitates calcium release from internal stores through the inositol 1,4,5-trisphosphate receptor, was upregulated in both areas. Interestingly, angiotensin II receptor type 1 gene transcription was significantly upregulated in the infarcted and unchanged in the noninfarcted myocardium. Nuclear factor ĸappa B as a calcium-dependent transcription factor showed increased activity in the infarction zone. The β-adrenergic axis does not seem to be involved, as metoprolol treatment did not have a significant impact on any of these results. We conclude that region-specific upregulation of angiotensin II receptor type 1 is a major factor for increased atrial natriuretic peptide production in the infarcted anterior wall. This effect is most likely achieved through inositol 1,4,5-trisphosphate-mediated cytosolic calcium increase and subsequent nuclear factor ĸappa B activation, which is a known transcription factor for natriuretic peptides.