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Induction of cardiac angiotensin I-converting enzyme with dietary NaCl-loading in genetically hypertensive and normotensive rats

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Abstract

We have recently shown that the angiotensin I converting enzyme (ACE) gene is linked to NaCl-loaded blood pressure in the stroke-prone spontaneously hypertensive rat (SHRSP), and that high-NaCl loading selectively stimulates ACE in the aorta of SHRSP but not in normotensive Wistar-Kyoto (WKY) rats. We therefore investigated the relationship between cardiac ACE and the development of hypertension and left ventricular hypertrophy in response to normal- and high-NaCl diet in these rats. ACE mRNA and ACE activity were measured in left ventricular tissue after completion of hemodynamic characterization of the animals. While SHRSP rats increased blood pressure (P<0.0001) and heart rate (P<0.005) in response to high NaCl, blood pressure remained unchanged in WKY. Similarly, relative left ventricular weight increased only in SHRSP after high NaCl (P<0.002). A significant two- to threefold increase of cardiac ACE mRNA and fourfold stimulation of ACE enzyme activity in response to high NaCl was found in both WKY and SHRSP rats (P<0.005). The induction of ACE gene expression was significantly more pronounced in SHRSP compared to WKY (P<0.02), whereas no significant strain differences in left ventricular ACE activity were found after either normal- or high-NaCl diet. Thus, arterial blood pressure and left ventricular weight remained unchanged in the WKY rats despite the activation of left ventricular ACE activity after high-NaCl exposure. These results demonstrate that left ventricular ACE activity is equally upregulated in response to high-NaCl in the normotensive and hypertensive strain, independently from the development of hypertension. We conclude that the pretranslational induction of left ventricular ACE with high-NaCl loading may be important both for the regulation of cardiac angiotensins and kinins and for local therapeutic ACE inhibition in the heart during high-salt status.

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Abbreviations

ACE :

Angiotensin I-converting enzyme

Ang :

Angiotensin

LVH :

Left ventricular hypertrophy

PCR :

Polymerase chain reaction

SHRSP :

Stroke-prone spontaneously hypertensive rat

WKY :

Wistar-Kyoto

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Author notes

  1. R. Kreutz

    Present address: Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, 20 Shuttack Street, Thorn Building 1104, 02115-6195, Boston, MA, USA

Authors and Affiliations

  1. German Institute for High Blood Pressure Research and Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, D-69120, Heidelberg, Germany

    R. Kreutz, M. S. Fernandez-Alfonso & Y. Liu

  2. Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13122, Berlin-Buch, Germany

    D. Ganten & M. Paul

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  1. R. Kreutz
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  4. D. Ganten
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Kreutz, R., Fernandez-Alfonso, M.S., Liu, Y. et al. Induction of cardiac angiotensin I-converting enzyme with dietary NaCl-loading in genetically hypertensive and normotensive rats. J Mol Med 73, 243–248 (1995). https://doi.org/10.1007/BF00189924

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  • DOI: https://doi.org/10.1007/BF00189924

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