Endocrinology, Vol 137, 137-143, Copyright © 1996 by Endocrine Society

ARTICLES

Alpha 1-adrenergic stimulation of isolated rat atria results in discoordinate increases in natriuretic peptide secretion and gene expression and enhances Egr-1 and c-Myc expression

BG Bruneau, LA Piazza and AJ de Bold
University of Ottawa Heart Institute Research Center, Ottawa Civic Hospital, Ontario, Canada.

We studied the effects of alpha1-adrenergic stimulation on atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) secretion and gene expression in isolated right atria. The early-response genes Egr-1 and c-myc were also studied as potential markers of transcriptional activation after alpha1-adrenergic stimulation. Isolated right atria from rats were stimulated for up to 8 h by the alpha1-adrenergic agonist phenylephrine (PE). PE at 10, 50, or 100 microM stimulated the secretion of immunoreactive (ir) ANF, beginning at 0.5 h and peaking after 1.5 h, IrANF secretion remained significantly elevated for 8 h with 100 microM PE, reached control levels after 5 h with 10 microM PE, and after 6 h microM PE with 50 microM PE, PE at 50 or 100 microM stimulated irBNP secretion after 15 min, which peaked at 1 h, and thereafter remained above control levels. Calculation of irANF/irBNP ratios revealed that their stimulated secretion was not coregulated. PE caused significant changes in steady state transcript levels for the genes studied. After 6 h, 50 microM PE caused a 49% increase in ANF messenger RNA (mRNA) levels. BNP mRNA levels were increased by 135% after 6 h and by 77% after 8 h. Egr-1 mRNA levels were increased by 81% after 4 h, 167 after 6 h, and 40% after 8 h of treatment, mRNA levels of c-myc were increased by 49% after 4 h and 53% after 6 h. PE-induced increases in secretion and gene expression were inhibited by the alpha1-adrenergic receptor antagonist prozosin (10 microM). We conclude that both ANF and BNP secretion from atria can be stimulated by PE, and that their secretion is not coregulated. The kinetics of enhanced natriuretic peptide gene expression and secretion did not change in parallel, suggesting that these processes are not acutely coordinated. The enhanced expression of Egr-1 and c-myc suggests that they may be involved in the modulation of atrial gene expression in response to alpha1-adrenergic stimulation. The results presented suggest that compensatory adrenergic activation such as those seen in several clinical entities may be one of the factors that provide long-term enhanced natriuretic peptide production, thus contributing to the maintenance of cardiovascular homeostasis.

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