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 Marttila, M. Articles by Ruskoaho, H. Search for Related Content PubMed PubMed Citation Articles by Marttila, M. Articles by Ruskoaho, H. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

(Hypertension. 1996;28:995-1004.)
© 1996 American Heart Association, Inc.

Articles

Synthesis and Secretion of Natriuretic Peptides in the Hypertensive TGR(mREN-2)27 Transgenic Rat

Minna Marttila; Olli Vuolteenaho; Detlev Ganten; Kazuwa Nakao; Heikki Ruskoaho

the Departments of Pharmacology and Toxicology (M.M., H.R.) and Physiology (O.V.), Biocenter Oulu, University of Oulu (Finland); Max-Delbruck Center for Molecular Medicine, Berlin-Buch, Germany (D.G.); and the 2nd Department of Internal Medicine, Kyoto (Japan) University School of Medicine (K.N.).

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

To examine the pathophysiological mechanisms in transgenic rats carrying the murine Ren-2^d renin gene, we studied atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression and secretion in 12-week-old hypertensive TGR(mREN-2)27 and normotensive Sprague-Dawley rats. Hypertension and marked left ventricular hypertrophy in TGR(mREN-2)27 rats were associated with high baseline plasma levels of immunoreactive ANP (148±18 versus 34±3 pmol/L, hypertensive versus normotensive rats; P<.001), whereas plasma immunoreactive BNP levels did not differ significantly between the strains (19±4 versus 12±3 pmol/L, P=.06). ANP mRNA and immunoreactive ANP levels in the left ventricular endocardial and epicardial layers in TGR(mREN-2)27 rats were about 20 to 40 times higher (P<.001) than those in normotensive rats. There were no statistically significant differences between atrial and ventricular BNP mRNA levels, but left ventricular immunoreactive BNP concentrations were twofold higher in hypertensive TGR(mREN-2)27 than in normotensive rats. Infusion of [Arg⁸]-vasopressin (0.05 µg/kg per minute IV, for 2 hours) in normotensive rats produced rapid increases (twofold, P<.05 to .01) in left ventricular BNP mRNA and immunoreactive BNP levels, whereas ventricular BNP mRNA and peptide levels did not change significantly in hypertensive rats. The increase in left atrial BNP mRNA levels in response to acute pressure overload was also significantly smaller in the hypertensive than normotensive rats (3.5-fold versus 5.2-fold, P<.01). Furthermore, the proportional but not absolute (in picomoles per liter) increase in plasma immunoreactive ANP was smaller in transgenic rats in response to acute saline and [Arg⁸]-vasopressin infusions (0.9% NaCl: 1.9-fold increase versus 4.4-fold increase in normotensive rats, P<.001; [Arg⁸]-vasopressin: 2.2-fold versus 4.8-fold increase, P<.001). These results show that baseline and cardiac overload–induced increases in BNP synthesis are markedly attenuated in transgenic rats carrying the murine Ren-2^d renin gene. In addition, acute volume and pressure overload produced a smaller proportional increase in ANP secretion in hypertensive rats than normotensive rats. These alterations in the natriuretic peptide system may contribute to the pathogenesis of hypertension and cardiovascular complications in the TGR(mREN-2)27 rat.

Key Words: renin-angiotensin system • natriuretic peptides • renin • rats, transgenic • hormones • gene expression

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]

				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]

				R. Willenbrock, M. Scheuermann, G. Thibault, Markus Haass, K. Hohnel, J. Bohlender, F. C. Luft, and Rainer Dietz Angiotensin inhibition and atrial natriuretic peptide release after acute volume expansion in rats with aortocaval shunt Cardiovasc Res, June 1, 1999; 42(3): 733 - 742. [Abstract] [Full Text] [PDF]

				M. L Kuroski de Bold Estrogen, natriuretic peptides and the renin-angiotensin system Cardiovasc Res, March 1, 1999; 41(3): 524 - 531. [Abstract] [Full Text] [PDF]

				H. Hupf, D. Grimm, G. A. J. Riegger, and H. Schunkert Evidence for a Vasopressin System in the Rat Heart Circ. Res., February 19, 1999; 84(3): 365 - 370. [Abstract] [Full Text] [PDF]