EFFECTS OF INTERLEUKIN-1-BETA AND NITRIC-OXIDE ON CARDIAC MYOCYTES

Using cultured neonatal ventricular myocytes, we investigated whether nitric oxide (NO) directly influences myocyte growth. Treatment of myo cytes with phenylephrine stimulated growth, as indicated by increases in atrial natriuretic factor, brain natriuretic peptide (BNP) mRNA and BNP secretion, activator protein 1 activity (activation of early resp onse genes), and total cellular protein content. NO was stimulated by treatment of myocytes with interleukin-1 beta (IL-1 beta) or was gener ated by the NO donor nitroglycerin, and its effects on total protein c ontent and BNP secretion were measured. Treatment of cardiocytes with 3.4 nmol/L IL-1 beta for 24 hours stimulated NO (nitrite) production b y threefold, which resulted from an increase in the inducible isoform of NO synthase mRNA. Dexamethasone inhibited IL-1 beta induction of ni trite production, whereas the protein kinase C inhibitor staurosporine had no effect. IL-1 beta had no effect on either basal or phenylephri ne-stimulated protein content but inhibited phenylephrine-stimulated B NP secretion. Nitroglycerin (10(-7) to 10(-3) mol/L) dose-dependently increased NO production; however, only the highest dose (10(-3) mol/L) reduced basal and phenylephrine-stimulated total protein content and BNP secretion. cGMP, a second messenger of NO, had no effect on either basal or phenylephrine-stimulated BNP secretion or total protein cont ent. In conclusion, our data indicate that BNP mRNA is stimulated by p henylephrine as shown previously for atrial natriuretic factor. Althou gh both BNP and total protein content are increased by phenylephrine, these effects are not inhibited by NO. However, IL-1 beta inhibits phe nylephrine-stimulated BNP secretion but not total protein content, sug gesting that regulation of BNP secretion can be dissociated from total protein synthesis during myocyte growth.