The natriuretic, diuretic, and vasorelaxant hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are synthesized and secreted mainly from the mammalian atria of the heart, and are crucial for the maintenance of cardiovascular homeostasis. Direct stimulation of isolated adult rat atrial tissue by stretch, endothelin-1, and phenylephrine was conducted to attempt to define the mechanisms invoked in controlling the secretion and gene expression of ANF and BNP in adult atrial cardiocytes. These stimuli represent models for mechanical, autocrine/paracine, and neuroendocrine stimulation of the endocrine heart. The expression of the early response genes c-fos, c-jun, Egr-1, and c-myc were also studied, since they may regulate ANF or BNP gene expression. Isolated rat atria were stimulated by stretch, endothelin-1, or phenylephrine. Radioimmunoassay was used to measure levels of ANF and BNP, and Northern blotting was employed to measure changes in mRNA levels. Stretch resulted in a rapid and short-lived increase in the secretion of ANF and BNP. Calculation of the ratio of ANF to BNP suggested that this may be due to exocytosis of granules that contain both peptides, as well as granules that contain ANF only. Stretch selectively stimulated the expression of the BNP, c-fos, Egr-1, and c-myc genes. Endothelin-1 stimulated the secretion of ANF and BNP, following a time course that is distinct from that elicited by stretch: the increase in secretion was gradual, reached a plateau, and after a few hours returns towards basal levels. The patterns was similar for ANF and BNP, which suggests that they are co-secreted in response to this stimulus. Phenylephrine stimulated ANF and BNP secretion, but their stimulated secretion was not co-regulated. Endothelin-1 and phenylephrine stimulated BNP, Egr-1, and c-myc gene expression. Phenylephrine also modestly stimulated ANF gene expression. Changes in ANF and BNP mRNA levels were not coordinated with increased BNP secretion. The results show that ANF and BNP secretion and gene expression are distinctly regulated; this may be due to the relative abundance of each hormone and to partially different mechanisms of secretion for each. Therefore, mechanical and neuroendocrine stimuli contribute in different and specific manners to the modulation of the endocrine heart and hence to the maintenance of cardiovascular homeostasis.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/10154 |
| Date | January 1996 |
| Creators | Bruneau, Benoit Gaëtan. |
| Contributors | Bold, Adolfo J. de, |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 256 p. |
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