Genetic control of blood pressure and the angiotensinogen locus.

Published

Journal Article

Variants of the human angiotensinogen gene have been linked in some studies to increased circulating angiotensinogen levels and essential hypertension. To test for direct causality between genotypes at the angiotensinogen locus and blood pressures, we have studied mice carrying zero, one, two, three, or four functional copies of the murine wild-type angiotensinogen gene (Agt) at its normal chromosomal location. Plasma angiotensinogen levels increase progressively, although not linearly, from zero in the zero-copy animals to 145% of normal in the four-copy animals. Mice of all genotypes are normal at birth, but most zero-copy animals die before weaning. The kidneys of the zero-copy animals show pathological changes as adults, but the kidneys are normal in the other genotypes. One adult zero-copy male tested was fertile. The blood pressures of the one-copy through four-copy animals show significant and almost linear increases of approximately 8 mmHg per gene copy despite their normal compensatory mechanisms being intact. These results establish a direct causal relationship between Agt genotypes and blood pressures.

Full Text

Duke Authors

Cited Authors

  • Kim, HS; Krege, JH; Kluckman, KD; Hagaman, JR; Hodgin, JB; Best, CF; Jennette, JC; Coffman, TM; Maeda, N; Smithies, O

Published Date

  • March 1995

Published In

Volume / Issue

  • 92 / 7

Start / End Page

  • 2735 - 2739

PubMed ID

  • 7708716

Pubmed Central ID

  • 7708716

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.92.7.2735

Language

  • eng