Vascular damage without hypertension in transgenic rats expressing prorenin exclusively in the liver

M Veniant*, J Menard, P Bruneval, S D Morley, MF Gonzales, J Mullins

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We have developed a transgenic animal model to investigate the effects of overexpression of rat prorenin on the cardiovascular system. Two transgenic rat lines were generated in which rat prorenin expression was directed to the liver by a human al-antitrypsin promoter. Liver-specific expression was confirmed by RNase protection assay. Plasma prorenin concentrations in transgenic rats were increased 400-fold in the males of both lines but were increased only two- to threefold in the females, Thus, transgene expression exhibited sexual dimorphism, Blood pressures were not significantly higher in transgenic rats than in nontransgenic controls. The ratio of heart weight to body weight was greater in male transgenic rats than in the nontransgenic controls, Histological analysis revealed severe renal lesions and hypertrophic cardiomyocytes in transgenic males only. This transgenic model demonstrates a likely role of prorenin in the development of cardiac and renal pathology independent of hypertension. These animals will facilitate studies of the effects of blockade of the renin-angiotensin system and other pharmacological interventions on the development and treatment of cardiac, vascular, and renal lesions induced by changes in this system in the absence of chronic hypertension.

Original languageEnglish
Pages (from-to)1966-1970
Number of pages5
JournalJournal of Clinical Investigation
Volume98
Issue number9
DOIs
Publication statusPublished - 1 Nov 1996

Keywords

  • blood pressure
  • renin-angiotensin system
  • plasma renin concentration
  • left ventricular hypertrophy
  • nephroangiosclerosis
  • MOUSE REN-2 GENE
  • ALPHA-1-ANTITRYPSIN GENE
  • MYOCARDIAL-INFARCTION
  • RENIN
  • ANGIOTENSIN
  • PLASMA
  • IDENTIFICATION
  • ACTIVATION
  • INHIBITION
  • BINDING

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