Atrial (ANP) and brain natriuretic peptide (BNP) expression after myocardial infarction in sheep: ANP is synthesized by fibroblasts infiltrating the infarct.

Cardiac gene expression of atrial natriuretic peptide (ANP) and that of brain natriuretic peptide (BNP) are markedly elevated after myocardial infarction. The cellular distribution and temporal responses of ANP and BNP messenger RNA (mRNA) expression were compared by in situ hybridization for 5 weeks after left coronary artery ligation in sheep. Ligation resulted in highly reproducible, transmural, left ventricular infarcts. Within the infarct, ANP mRNA appeared from 7 days after ligation, whereas BNP expression was undetectable in the infarct at any time. The cells synthesizing ANP were shown by in situ hybridization and immunocytochemistry to be fibroblasts invading the infarct. The appearance of ANP expression coincided with the transition of these cells to the myofibroblast phenotype. Treatment of cultured cardiac fibroblasts with transforming growth factor-beta (10 ng/ml) induced the expression of alpha-smooth muscle actin, characteristic of the transformation to myofibroblasts, and raised ANP concentrations in the medium. In the surviving myocardium of the left ventricle, ANP and BNP expression increased in response to ligation, BNP mRNA was particularly strong at the lateral margins of the infarct. In both left and right atria, levels of BNP mRNA increased markedly over the first 18 h, whereas levels of atrial ANP mRNA decreased over 3 days after infarction. This is the first report of ANP expression and synthesis by cardiac fibroblasts invading the fibrotic scar, suggesting that ANP may be involved in regulating fibroblast proliferation during reparative fibrosis.

The sites of gene expression of atrial, brain, and C-type natriuretic peptides in mouse fetal development: temporal changes in embryos and placenta.

Atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) belong to a family of hormones important in blood pressure and sodium homeostasis. Expression of ANP has been reported in embryo hearts, but BNP and CNP expression during development has not been described. We used in situ hybridization to identify the sites of gene expression of ANP, BNP, and CNP during development in mouse embryos at daily intervals from midgestation. Very intense expression of ANP and BNP was visible in the heart from 9.5 days gestation; levels of expression of both peptides in the ventricle exceeded those in atria throughout gestation. There was a major peak of atrial and ventricular ANP and BNP expression at 12.5 days, attaining levels similar to those in adult heart and then declining until birth. Cardiac expression of CNP was undetectable. Expression of ANP and CNP was also observed in distinct sites in the brain, and all three peptides were expressed in the spinal cord. In mouse placenta, strong CNP expression was seen in the decidua basalis around the large maternal blood vessels, and BNP message was detected at the peripheral margin of the decidual layer. This pattern of expression indicates that ANP and CNP are present during development of the mouse central nervous system and suggests that CNP and BNP participate in regulating the maternal blood supply to the developing embryo.