1. J Biol Chem. 2009 Jun 5;284(23):15564-72. doi: 10.1074/jbc.M806584200. Epub 2009
Mar 23.
Angiotensin-converting enzyme is a modifier of hypertensive end organ damage.
Liu X(1), Bellamy CO, Bailey MA, Mullins LJ, Dunbar DR, Kenyon CJ, Brooker G,
Kantachuvesiri S, Maratou K, Ashek A, Clark AF, Fleming S, Mullins JJ.
Author information:
(1)Molecular Physiology Laboratory, Centre for Cardiovascular Science, Queen's
Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United
Kingdom.
Severe forms of hypertension are characterized by high blood pressure combined
with end organ damage. Through the development and refinement of a transgenic rat
model of malignant hypertension incorporating the mouse renin gene, we previously
identified a quantitative trait locus on chromosome 10, which affects malignant
hypertension severity and morbidity. We next generated an inducible malignant
hypertensive model where the timing, severity, and duration of hypertension was
placed under the control of the researcher, allowing development of and recovery
from end organ damage to be investigated. We have now generated novel consomic
Lewis and Fischer rat strains with inducible hypertension and additional strains
that are reciprocally congenic for the refined chromosome 10 quantitative trait
locus. We have captured a modifier of end organ damage within the congenic region
and, using a range of bioinformatic, biochemical and molecular biological
techniques, have identified angiotensin-converting enzyme as the modifier of
hypertension-induced tissue microvascular injury. Reciprocal differences between
angiotensin-converting enzyme and the anti-inflammatory tetrapeptide,
N-acetyl-Ser-Asp-Lys-Pro in the kidney, a tissue susceptible to end organ damage,
suggest a mechanism for the amelioration of hypertension-dependent damage.
PMCID: PMC2708853
PMID: 19307186 [PubMed - indexed for MEDLINE]
PUBMED: 19307186
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