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

We studied the effects of alpha(1)-adrenergic stimulation on atrial na triuretic factor (ANF) and brain natriuretic peptide (BNP) secretion a nd gene expression in isolated right atria. The early-response genes E gr-1 and c-myc were also studied as potential markers of transcription al activation after alpha(1)-adrenergic stimulation. Isolated right at ria from rats were stimulated for up to 8 h by the alpha(1)-adrenergic agonist phenylephrine (PE). PE at 10, 50, or 100 mu M stimulated the secretion of immunoreactive (ir) ANF, beginning at 0.5 h and peaking a fter 1.5 h. IrANF secretion remained significantly elevated for 8 h wi th 100 mu M PE, reached control levels after 5 h with 10 mu M PE, and after 6 h with 50 mu M PE. PE at 50 or 100 mu M stimulated irBNP secre tion after 15 min, which peaked at 1 h, and thereafter remained above control levels. Calculation of irANF/irBhTP ratios revealed that their stimulated secretion was not coregulated. PE caused significant chang es in steady state transcript levels for the genes studied. After 6 h, 50 mu MPE caused a 49% increase in ANF messenger RNA (mRNA) levels. B NP 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 g ene expression mere inhibited by the alpha(1)-adrenergic receptor anta gonist prazosin (10 mu M). We conclude that both ANF and BNP secretion from atria can be stimulated by PE, and that their secretion is not c oregulated. The kinetics of enhanced natriuretic peptide gene expressi on and secretion did not change in parallel, suggesting that these pro cesses are not acutely coordinated. The enhanced expression of Egr-1 a nd c-myc suggests that they may be involved in the modulation of atria l gene expression in response to alpha(1)-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 c ontributing to the maintenance of cardiovascular homeostasis.