PMID: 8587401Jan 1, 1995Paper

Regulation of the endothelin system in transgenic rats expressing the human endothelin-2 gene

Journal of Cardiovascular Pharmacology
L LiefeldtM Paul

Abstract

We have established a transgenic rat model for the expression of the human endothelin-2 (ET-2). These animals exhibit overexpression of the transgene in tissues as well as in plasma. Despite these changes, blood pressure remains normal. To understand the regulatory mechanisms for normotension in the presence of increased ET-2 levels, we have investigated the ET system in more detail. We used competitive reverse transcription-polymerase chain reaction (RT-PCR) to evaluate possible overexpression or downregulation of endothelin A and B receptors at the mRNA level. PCR analyses revealed no significant differences of ETA and ETB receptor expression. In conclusion, the expression of human ET-2 in transgenic rats does not result in hypertension. Normotension in the transgenic animals is independent of ET receptor regulation. The reason for this may be counterregulation by other vasoactive systems, such as the NO system. Future studies will take this into account and will also concentrate on possible histomorphologic alterations caused by mitogenic properties of the endothelins.

Citations

Jan 1, 1997·Cardiovascular Drugs and Therapy·C Rosendorff
Jul 1, 1996·Transgenic Research·B CharreauI Anegon
Feb 19, 1999·Lancet·A Benigni, G Remuzzi
Jan 1, 1996·Pharmacology & Therapeutics·G A Gray, D J Webb
Apr 12, 2000·Kidney International·A Benigni
Oct 27, 2004·Expert Opinion on Investigational Drugs·Ariela BenigniGiuseppe Remuzzi
Mar 10, 2016·Pharmacological Reviews·Anthony P DavenportJanet J Maguire

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