The hypertensive Ren-2 transgenic rat TGR(mREN2)27 in hypertension research: Characteristics and functional aspects

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

  • Matthias Langheinrich - , Charité – Universitätsmedizin Berlin (Author)
  • Min Ae Lee - , Max Delbrück Center for Molecular Medicine (MDC), Free University of Berlin, Charité – Universitätsmedizin Berlin (Author)
  • Michael Böhm - , University of Cologne (Author)
  • Yigal M. Pinto - (Author)
  • Detlev Ganten - (Author)
  • Martin Paul - , Charité – Universitätsmedizin Berlin (Author)

Abstract

Primary human hypertension is a polygenic disorder. It is the prevalent cause of cardiovascular disease leading to cardiac failure, stroke, chronic renal failure and, ultimately, to death. Several genes are involved in cardiovascular control mechanisms and their genetics are complex. Experimental models which are well defined are needed to clarify the role of individual genes. The generation of the hypertensive transgenic rat line TGR(mREN2)27 bearing the murine Ren-2 gene cloned from the DBA/2J mouse strain provides a monogenic model of hypertension in which the genetic basis (the additional renin gene) is known. These rats develop severe hypertension, which reaches 200 mm Hg and higher at 8 weeks of age in the heterozygous animal. Homozygous rats develop even higher blood pressures than heterozygous animals, which is paralleled by a higher mortality rate in homozygous rats. Animals develop pathomorphologic alterations which are characteristic for systemic hypertension. The transgenic rats are characterized by unchanged or even suppressed concentrations of active renin, angiotensin I (ANG I), ANG II, and angiotensinogen compared to transgene-negative littermates. In contrast, plasma levels of inactive renin (prorenin) are much higher in TGR(mREN2)27 rats than in control animals. In the kidneys, renin is suppressed, probably mediated through negative feedback inhibition, in other tissues, especially in the adrenal gland, murine Ren-2 mRNA is expressed at very high levels. The cascade of pathophysiologic events which finally lead to hypertension is not fully understood in this rat model. Treatment with ACE inhibitors or angiotensin II receptor antagonists such as losartan is extremely efficient, which could mean that hypertension in this model is mediated through ANG II. Since the the renin-angiotensin system (RAS) in the kidneys is suppressed, other ANG II generating sites must be considered. This favors the concept of extrarenal RASs in this model. Am J Hypertens 1996;9:506-512.

Details

Original languageEnglish
Pages (from-to)506-512
Number of pages7
JournalAmerican journal of hypertension : AJH
Volume9
Issue number5
Publication statusPublished - May 1996
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 8735183

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • Cardiovascular system, Hypertension, Molecular biology, Renin-angiotensin system, Transgenic rats