Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A.

Published

Journal Article

Natriuretic peptides, produced in the heart, bind to the natriuretic peptide receptor A (NPRA) and cause vasodilation and natriuresis important in the regulation of blood pressure. We here report that mice lacking a functional Npr1 gene coding for NPRA have elevated blood pressures and hearts exhibiting marked hypertrophy with interstitial fibrosis resembling that seen in human hypertensive heart disease. Echocardiographic evaluation of the mice demonstrated a compensated state of systemic hypertension in which cardiac hypertrophy and dilatation are evident but with no reduction in ventricular performance. Nevertheless, sudden death, with morphologic evidence indicative in some animals of congestive heart failure and in others of aortic dissection, occurred in all 15 male mice lacking Npr1 before 6 months of age, and in one of 16 females in our study. Thus complete absence of NPRA causes hypertension in mice and leads to cardiac hypertrophy and, particularly in males, lethal vascular events similar to those seen in untreated human hypertensive patients.

Full Text

Duke Authors

Cited Authors

  • Oliver, PM; Fox, JE; Kim, R; Rockman, HA; Kim, HS; Reddick, RL; Pandey, KN; Milgram, SL; Smithies, O; Maeda, N

Published Date

  • December 1997

Published In

Volume / Issue

  • 94 / 26

Start / End Page

  • 14730 - 14735

PubMed ID

  • 9405681

Pubmed Central ID

  • 9405681

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.94.26.14730

Language

  • eng