This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Magga, J. Articles by Ruskoaho, H. Search for Related Content PubMed PubMed Citation Articles by Magga, J. Articles by Ruskoaho, H.

(Circulation Research. 1997;81:694-702.)
© 1997 American Heart Association, Inc.

Articles

Involvement of Transcriptional and Posttranscriptional Mechanisms in Cardiac Overload–Induced Increase of B-Type Natriuretic Peptide Gene Expression

Jarkko Magga, Olli Vuolteenaho, Heikki Tokola, Minna Marttila, , Heikki Ruskoaho

From the Department of Pharmacology and Toxicology (J.M., H.T., M.M., H.R.) and Physiology (O.V.), Biocenter Oulu, University of Oulu (Finland).

Correspondence to Heikki Ruskoaho, MD, Department of Pharmacology and Toxicology, University of Oulu, Kajaanintie 52 D, FIN-90220 Oulu, Finland. E-mail heikki.ruskoaho{at}oulu.fi

Abstract The induction of atrial and ventricular B-type natriuretic peptide (BNP) gene expression is one of the earliest events occurring during hemodynamic overload. To examine the molecular mechanisms for increased BNP gene expression during cardiac overload, we studied the induction of the BNP gene expression compared with that of atrial natriuretic peptide (ANP) in a modified perfused rat heart preparation. An increase in right atrial pressure of 5 mm Hg resulted in a 1.4-fold (P<.05) and 2.2-fold (P<.01) increase in BNP mRNA levels after 1 and 2 hours, respectively, whereas ANP mRNA levels remained unchanged. Stretching for up to 2 hours also significantly increased right atrial immunoreactive BNP (ir-BNP) levels (from 15.8±2.2 to 20.1±1.2 ng/mg, P<.05). Actinomycin D (10 µg/mL), a transcriptional inhibitor, completely inhibited the stretch-induced increase in atrial BNP mRNA levels at 1 hour (P<.05) and 2 hours (P<.001), whereas a protein synthesis inhibitor, cycloheximide (90 µg/mL), had no effect on basal or direct mechanical stretch-induced increase in right atrial BNP mRNA levels. Furthermore, we examined the role of tyrosine kinase and protein kinase C activities in acute mechanical stretch–induced increase in BNP synthesis. Tyrosine kinase inhibitors lavendustin A (1 µmol/L) and tyrphostin A25 (3 µmol/L) and protein kinase C inhibitors staurosporine (30 nmol/L) and chelerythrine (1 µmol/L) prevented the stretch-induced increase in right atrial ir-BNP concentrations at 2 hours. In addition, chelerythrine inhibited the increase of right atrial BNP mRNA levels stimulated by cardiac overload. These results demonstrate that the early increase of BNP mRNA levels by mechanical stretch results from increased transcriptional activation and is independent of protein synthesis. Our results also suggest that protein kinase C and tyrosine kinases activities may be involved in coupling cardiac overload to alterations in atrial BNP synthesis.

Key Words: cardiac gene expression • mechanical load • natriuretic peptide • transcription

This article has been cited by other articles:

				H. Ruskoaho Cardiac Hormones as Diagnostic Tools in Heart Failure Endocr. Rev., June 1, 2003; 24(3): 341 - 356. [Abstract] [Full Text] [PDF]

				V. Tervonen, H. Ruskoaho, T. Lecklin, M. Ilves, and O. Vuolteenaho Salmon cardiac natriuretic peptide is a volume-regulating hormone Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E353 - E361. [Abstract] [Full Text] [PDF]

				M. Marttila, N. Hautala, P. Paradis, M. Toth, O. Vuolteenaho, M. Nemer, and H. Ruskoaho GATA4 Mediates Activation of the B-Type Natriuretic Peptide Gene Expression in Response to Hemodynamic Stress Endocrinology, November 1, 2001; 142(11): 4693 - 4700. [Abstract] [Full Text] [PDF]

				G. M. Bialik, Z. A. Abassi, I. Hammel, J. Winaver, and D. Lewinson Evaluation of Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Atrial Granules of Rats with Experimental Congestive Heart Failure J. Histochem. Cytochem., October 1, 2001; 49(10): 1293 - 1300. [Abstract] [Full Text] [PDF]

				T. Walther, H. Stepan, and R. Faber Dual natriuretic peptide response to volume load in the fetal circulation Cardiovasc Res, March 1, 2001; 49(4): 817 - 819. [Abstract] [Full Text] [PDF]

				T. Langenickel, I. Pagel, K. Hohnel, R. Dietz, and R. Willenbrock Differential regulation of cardiac ANP and BNP mRNA in different stages of experimental heart failure Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1500 - H1506. [Abstract] [Full Text] [PDF]

				P. Taskinen, M. Toth, O. Vuolteenaho, J. Magga, and H. Ruskoaho Inhibition of Atrial Wall Stretch-Induced Cardiac Hormone Secretion by Lavendustin A, a Potent Tyrosine Kinase Inhibitor Endocrinology, September 1, 1999; 140(9): 4198 - 4207. [Abstract] [Full Text]