Angiotensin-converting enzyme Ii a modifier of hypertensive end organ damage

Xiaojun Liu, Christopher O. C. Bellamy, Matthew A. Bailey, Linda J. Mullins, Donald R. Dunbar, Christopher J. Kenyon, Gillian Brooker, Surasak Kantachuvesiri, Klio Maratou, Ali Ashek, Allan F. Clark, Stewart Fleming, John J. Mullins

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    18 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)15564-15572
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume284
    Issue number23
    DOIs
    Publication statusPublished - 5 Jun 2009

    Keywords

    • CYP1A1-REN2 TRANSGENIC RATS
    • DEPENDENT MALIGNANT HYPERTENSION
    • TERMINAL CATALYTIC DOMAIN
    • ASP-LYS-PRO
    • BLOOD-PRESSURE
    • PHASE HYPERTENSION
    • NITRIC-OXIDE
    • AC-SDKP
    • GENE
    • TGR(MREN2)27

    Cite this

    Liu, X., Bellamy, C. O. C., Bailey, M. A., Mullins, L. J., Dunbar, D. R., Kenyon, C. J., Brooker, G., Kantachuvesiri, S., Maratou, K., Ashek, A., Clark, A. F., Fleming, S., & Mullins, J. J. (2009). Angiotensin-converting enzyme Ii a modifier of hypertensive end organ damage. Journal of Biological Chemistry, 284(23), 15564-15572. https://doi.org/10.1074/jbc.M806584200