The infarction zone rather than the non-infarcted remodeling zone over-expresses angiotensin II receptor type 1 and is the main source of ventricular atrial natriuretic peptide

Abstract Chromogranin B and inositol 1,4,5-trishphosphate 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 non-infarcted myocardium and moreover under treatment with metoprolol. We found that atrial natriuretic peptide gene transcription was significantly more elevated in the infarcted compared to the non-infarcted myocardium. Chromogranin B, which facilitates calcium release from internal stores through the inositol 1,4,5-trisphosphate receptor, was up-regulated in both areas. Interestingly, angiotensin II receptor type 1 gene transcription was significantly up-regulated in the infarcted and unchanged in the non-infarcted myocardium. Nuclear factor (NF)-ĸB as a calcium dependent transcription factor showed increased activity in the infarction zone. The s-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 up-regulation 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 NF-ĸB activation, which is a known transcription factor for natriuretic peptides.