Skip to main content

Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice.

Publication ,  Journal Article
Knowles, JW; Esposito, G; Mao, L; Hagaman, JR; Fox, JE; Smithies, O; Rockman, HA; Maeda, N
Published in: J Clin Invest
April 2001

Mice lacking natriuretic peptide receptor A (NPRA) have marked cardiac hypertrophy and chamber dilatation disproportionate to their increased blood pressure (BP), suggesting, in support of previous in vitro data, that the NPRA system moderates the cardiac response to hypertrophic stimuli. Here, we have followed the changes in cardiac function in response to altered mechanical load on the heart of NPRA-null mice (Npr1-/-). Chronic treatment with either enalapril, furosemide, hydralazine, or losartan were all effective in reducing and maintaining BP at normal levels without affecting heart weight/body weight. In the reverse direction, we used transverse aortic constriction (TAC) to induce pressure overload. In the Npr1-/- mice, TAC resulted in a 15-fold increase in atrial natriuretic peptide (ANP) expression, a 55% increase in left ventricular weight/body weight (LV/BW), dilatation of the LV, and significant decline in cardiac function. In contrast, banded Npr1+/+ mice showed only a threefold increase in ANP expression, an 11% increase in LV/BW, a 0.2 mm decrease in LV end diastolic dimension, and no change in fractional shortening. The activation of mitogen-activated protein kinases that occurs in response to TAC did not differ in the Npr1+/+ and Npr1-/- mice. Taken together, these results suggest that the NPRA system has direct antihypertrophic actions in the heart, independent of its role in BP control.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

April 2001

Volume

107

Issue

8

Start / End Page

975 / 984

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Telemetry
  • Receptors, Atrial Natriuretic Factor
  • Propranolol
  • Organ Size
  • Myocardium
  • Mitogen-Activated Protein Kinases
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Knowles, J. W., Esposito, G., Mao, L., Hagaman, J. R., Fox, J. E., Smithies, O., … Maeda, N. (2001). Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice. J Clin Invest, 107(8), 975–984. https://doi.org/10.1172/JCI11273
Knowles, J. W., G. Esposito, L. Mao, J. R. Hagaman, J. E. Fox, O. Smithies, H. A. Rockman, and N. Maeda. “Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice.J Clin Invest 107, no. 8 (April 2001): 975–84. https://doi.org/10.1172/JCI11273.
Knowles JW, Esposito G, Mao L, Hagaman JR, Fox JE, Smithies O, et al. Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice. J Clin Invest. 2001 Apr;107(8):975–84.
Knowles, J. W., et al. “Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice.J Clin Invest, vol. 107, no. 8, Apr. 2001, pp. 975–84. Pubmed, doi:10.1172/JCI11273.
Knowles JW, Esposito G, Mao L, Hagaman JR, Fox JE, Smithies O, Rockman HA, Maeda N. Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice. J Clin Invest. 2001 Apr;107(8):975–984.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

April 2001

Volume

107

Issue

8

Start / End Page

975 / 984

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Telemetry
  • Receptors, Atrial Natriuretic Factor
  • Propranolol
  • Organ Size
  • Myocardium
  • Mitogen-Activated Protein Kinases
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice