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. 1997;96:3053-3062.)
© 1997 American Heart Association, Inc.

Articles

Endothelin-1 Is Involved in Stretch-Induced Early Activation of B-Type Natriuretic Peptide Gene Expression in Atrial but Not in Ventricular Myocytes

Acute Effects of Mixed ET_A/ET_B and AT₁ Receptor Antagonists In Vivo and In Vitro

Jarkko Magga, MD; Olli Vuolteenaho, MD, PhD; Minna Marttila, MD; ; Heikki Ruskoaho, MD, PhD

From the Department of Pharmacology and Toxicology and the Department of 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

Background The precise role of paracrine and autocrine factors in mechanical load–induced activation of cardiac gene expression is unknown. Here we report the effects of endothelin-1 (ET-1) and angiotensin II (Ang II) receptor antagonism on acute pressure overload–induced activation of cardiac B-type natriuretic peptide (BNP) gene expression in spontaneously hypertensive rats (SHRs) in vivo and on mechanical stretch–induced increase in atrial BNP gene expression in vitro.

Methods and Results Acute pressure overload produced in conscious SHRs by infusion of arginine⁸-vasopressin (0.05 µg · kg^-1 · min^-1) for 2 hours resulted in an increase in BNP mRNA levels in the left ventricle as well as in the atrium. Bolus injections of bosentan (mixed ET_A/ET_B receptor antagonist, 10 mg/kg IV) but not losartan (AT₁ receptor antagonist, 10 mg/kg IV) blocked the increase of the BNP mRNA levels produced by pressure overload in the left atria, whereas the elevation of BNP mRNA levels was similar (a 1.9-fold increase) in the left ventricles of vehicle-, losartan-, and bosentan-infused SHRs. In an isolated perfused rat heart preparation, infusion of bosentan (1 µmol/L) for 2 hours inhibited the mechanical stretch–induced increase in BNP mRNA levels in the right atria, whereas an AT₁ receptor antagonist, CV-11974 (10 nmol/L), had no effect.

Conclusions The findings of the present study demonstrate that Ang II and ET-1 are not obligatorily required for stretch to trigger the increased BNP gene expression in ventricular myocytes in vivo. In contrast, mechanical load on the atrial myocytes did initiate an ET-1–dependent expression of BNP gene showing that endogenous ET-1 production differentially regulates BNP gene expression in atrial and ventricular myocytes.

Key Words: pressure • natriuretic peptides • endothelin • angiotensin • hypertrophy

This article has been cited by other articles:

				D. Bonderman, R. Nowotny, N. Skoro-Sajer, J. Jakowitsch, C. Adlbrecht, W. Klepetko, and I. M. Lang Bosentan Therapy for Inoperable Chronic Thromboembolic Pulmonary Hypertension Chest, October 1, 2005; 128(4): 2599 - 2603. [Abstract] [Full Text] [PDF]

				O. Tenhunen, B. Sarman, R. Kerkela, I. Szokodi, L. Papp, M. Toth, and H. Ruskoaho Mitogen-activated Protein Kinases p38 and ERK 1/2 Mediate the Wall Stress-induced Activation of GATA-4 Binding in Adult Heart J. Biol. Chem., June 4, 2004; 279(23): 24852 - 24860. [Abstract] [Full Text] [PDF]

				M. Luodonpaa, H. Leskinen, M. Ilves, O. Vuolteenaho, and H. Ruskoaho Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1085 - R1092. [Abstract] [Full Text] [PDF]

				S. Pikkarainen, H. Tokola, T. Majalahti-Palviainen, R. Kerkela, N. Hautala, S. S. Bhalla, F. Charron, M. Nemer, O. Vuolteenaho, and H. Ruskoaho GATA-4 Is a Nuclear Mediator of Mechanical Stretch-activated Hypertrophic Program J. Biol. Chem., June 20, 2003; 278(26): 23807 - 23816. [Abstract] [Full Text] [PDF]

				J. Piuhola, M. Makinen, I. Szokodi, and H. Ruskoaho Dual role of endothelin-1 via ETA and ETB receptors in regulation of cardiac contractile function in mice Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H112 - H118. [Abstract] [Full Text] [PDF]

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

				M. H. Freitag, M. G. Larson, D. Levy, E. J. Benjamin, T. J. Wang, E. P. Leip, P. W.F. Wilson, and R. S. Vasan Plasma Brain Natriuretic Peptide Levels and Blood Pressure Tracking in the Framingham Heart Study Hypertension, April 1, 2003; 41(4): 978 - 983. [Abstract] [Full Text] [PDF]

				J. Piuhola, I. Szokodi, P. Kinnunen, M. Ilves, R. deChatel, O. Vuolteenaho, and H. Ruskoaho Endothelin-1 Contributes to the Frank-Starling Response in Hypertrophic Rat Hearts Hypertension, January 1, 2003; 41(1): 93 - 98. [Abstract] [Full Text] [PDF]

				I. Szokodi, P. Tavi, G. Foldes, S. Voutilainen-Myllyla, M. Ilves, H. Tokola, S. Pikkarainen, J. Piuhola, J. Rysa, M. Toth, et al. Apelin, the Novel Endogenous Ligand of the Orphan Receptor APJ, Regulates Cardiac Contractility Circ. Res., September 6, 2002; 91(5): 434 - 440. [Abstract] [Full Text] [PDF]

				M. Suo, N. Hautala, G. Foldes, I. Szokodi, M. Toth, H. Leskinen, P. Uusimaa, O. Vuolteenaho, M. Nemer, and H. Ruskoaho Posttranscriptional Control of BNP Gene Expression in Angiotensin II-Induced Hypertension Hypertension, March 1, 2002; 39(3): 803 - 808. [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. Foldes, M. Suo, I. Szokodi, Z. Lako-Futo, R. deChatel, O. Vuolteenaho, P. Huttunen, H. Ruskoaho, and M. Toth Factors Derived from Adrenals Are Required for Activation of Cardiac Gene Expression in Angiotensin II-Induced Hypertension Endocrinology, October 1, 2001; 142(10): 4256 - 4263. [Abstract] [Full Text] [PDF]

				J. Piuhola, A. Hammes, K. Schuh, L. Neyses, O. Vuolteenaho, and H. Ruskoaho Overexpression of sarcolemmal calcium pump attenuates induction of cardiac gene expression in response to ET-1 Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2001; 281(3): R699 - R705. [Abstract] [Full Text] [PDF]

				P. Kinnunen, J. Piuhola, H. Ruskoaho, and I. Szokodi AM reverses pressor response to ET-1 independently of NO in rat coronary circulation Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1178 - H1183. [Abstract] [Full Text] [PDF]

				N. Hautala, H. Tokola, M. Luodonpaa, J. Puhakka, H. Romppanen, O. Vuolteenaho, and H. Ruskoaho Pressure Overload Increases GATA4 Binding Activity via Endothelin-1 Circulation, February 6, 2001; 103(5): 730 - 735. [Abstract] [Full Text] [PDF]

				L. Eklund, J. Piuhola, J. Komulainen, R. Sormunen, C. Ongvarrasopone, R. Fässler, A. Muona, M. Ilves, H. Ruskoaho, T. E. S. Takala, et al. Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice PNAS, January 23, 2001; (2001) 31444798. [Abstract] [Full Text]

				H. Romppanen, J. Puhakka, G. Foldes, I. Szokodi, O. Vuolteenaho, H. Tokola, M. Toth, and H. Ruskoaho Endothelin-1-Independent and Angiotensin II-Independent Induction of Adrenomedullin Gene Expression Hypertension, January 1, 2001; 37(1): 84 - 90. [Abstract] [Full Text] [PDF]

				C. J. Pemberton, M. L. Johnson, T. G. Yandle, and E. A. Espiner Deconvolution Analysis of Cardiac Natriuretic Peptides During Acute Volume Overload Hypertension, September 1, 2000; 36(3): 355 - 359. [Abstract] [Full Text] [PDF]

				P. Kinnunen, I. Szokodi, M. G. Nicholls, and H. Ruskoaho Impact of NO on ET-1- and AM-induced inotropic responses: potentiation by combined administration Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2000; 279(2): R569 - R575. [Abstract] [Full Text] [PDF]

				K. Kokkonen, H. Vierimaa, S. Bergstrom, V. Tervonen, O. Arjamaa, H. Ruskoaho, M. Jarvilehto, and O. Vuolteenaho Novel salmon cardiac peptide hormone is released from the ventricle by regulated secretory pathway Am J Physiol Endocrinol Metab, February 1, 2000; 278(2): E285 - E292. [Abstract] [Full Text] [PDF]

				L. Eklund, J. Piuhola, J. Komulainen, R. Sormunen, C. Ongvarrasopone, R. Fassler, A. Muona, M. Ilves, H. Ruskoaho, T. E. S. Takala, et al. Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice PNAS, January 30, 2001; 98(3): 1194 - 1199. [Abstract] [Full Text] [PDF]