(Hypertension. 1995;25:421-430.)
© 1995 American Heart Association, Inc.
Articles |
Effects of Interleukin-1ß and Nitric Oxide on Cardiac Myocytes
From the Hypertension and Vascular Research Division, Henry Ford Health Sciences Center, Detroit, Mich.
Abstract Using cultured neonatal ventricular myocytes, we investigated whether nitric oxide (NO) directly influences myocyte growth. Treatment of myocytes 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-response genes), and total cellular protein content. NO was stimulated by treatment of myocytes with interleukin-1ß (IL-1ß) or was generated by the NO donor nitroglycerin, and its effects on total protein content and BNP secretion were measured. Treatment of cardiocytes with 3.4 nmol/L IL-1ß for 24 hours stimulated NO (nitrite) production by threefold, which resulted from an increase in the inducible isoform of NO synthase mRNA. Dexamethasone inhibited IL-1ß induction of nitrite production, whereas the protein kinase C inhibitor staurosporine had no effect. IL-1ß had no effect on either basal or phenylephrine-stimulated protein content but inhibited phenylephrine-stimulated BNP 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 content. In conclusion, our data indicate that BNP mRNA is stimulated by phenylephrine as shown previously for atrial natriuretic factor. Although both BNP and total protein content are increased by phenylephrine, these effects are not inhibited by NO. However, IL-1ß inhibits phenylephrine-stimulated BNP secretion but not total protein content, suggesting that regulation of BNP secretion can be dissociated from total protein synthesis during myocyte growth.
Key Words: brain natriuretic peptide • heart hypertrophy • interleukins • cytokines • nitric oxide • muscle, cardiac
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