A genetic model of malignant phase hypertension in rats

Caroline E. Whitworth, Stewart Fleming, Yuri Kotelevtsev, Lynn Manson, Gillian A. Brooker, Allan D. Cumming, John J. Mullins

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    31 Citations (Scopus)

    Abstract

    A genetic model of malignant phase hypertension in rats is described which closely parallels the natural history of untreated human malignant phase hypertension. Although the factors initiating transition from essential hypertension to the accelerated phase in humans remain unknown, we report the characteristics of a genetically determined and reproducible phenotype which was found to result from a cross between hypertensive transgenic Ren-2 rats and normotensive Sprague-Dawley (Edinburgh) rats. Male F1 hybrids developed malignant phase hypertension with a penetrance of 73.5% (95% confidence limits 65.7 to 81.3%) by 100 days of age. Phenotypic features included an accelerated rise in blood pressure, fibrinoid necrosis, activation of the renal renin-angiotensin system and microangiopathic hemolytic anemia. In an analytical cross no significant difference in blood pressure was observed between malignant phase and non-malignant phase animals prior to transition, implying that a factor in addition to hypertension appears necessary for inducing transition to the malignant phase phenotype. Segregation of the malignant phenotype suggested that susceptibility is determined by at most two genetic loci.
    Original languageEnglish
    Pages (from-to)529-35
    Number of pages7
    JournalKidney International
    Volume47
    Issue number2
    DOIs
    Publication statusPublished - 1995

    Fingerprint

    Malignant Hypertension
    Genetic Models
    Phenotype
    Blood Pressure
    Genetic Loci
    Penetrance
    Hemolytic Anemia
    Renin-Angiotensin System
    Sprague Dawley Rats
    Necrosis
    Hypertension
    Kidney

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    Whitworth, C. E., Fleming, S., Kotelevtsev, Y., Manson, L., Brooker, G. A., Cumming, A. D., & Mullins, J. J. (1995). A genetic model of malignant phase hypertension in rats. Kidney International, 47(2), 529-35. https://doi.org/10.1038/ki.1995.66
    Whitworth, Caroline E. ; Fleming, Stewart ; Kotelevtsev, Yuri ; Manson, Lynn ; Brooker, Gillian A. ; Cumming, Allan D. ; Mullins, John J. / A genetic model of malignant phase hypertension in rats. In: Kidney International. 1995 ; Vol. 47, No. 2. pp. 529-35.
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    abstract = "A genetic model of malignant phase hypertension in rats is described which closely parallels the natural history of untreated human malignant phase hypertension. Although the factors initiating transition from essential hypertension to the accelerated phase in humans remain unknown, we report the characteristics of a genetically determined and reproducible phenotype which was found to result from a cross between hypertensive transgenic Ren-2 rats and normotensive Sprague-Dawley (Edinburgh) rats. Male F1 hybrids developed malignant phase hypertension with a penetrance of 73.5{\%} (95{\%} confidence limits 65.7 to 81.3{\%}) by 100 days of age. Phenotypic features included an accelerated rise in blood pressure, fibrinoid necrosis, activation of the renal renin-angiotensin system and microangiopathic hemolytic anemia. In an analytical cross no significant difference in blood pressure was observed between malignant phase and non-malignant phase animals prior to transition, implying that a factor in addition to hypertension appears necessary for inducing transition to the malignant phase phenotype. Segregation of the malignant phenotype suggested that susceptibility is determined by at most two genetic loci.",
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    Whitworth, CE, Fleming, S, Kotelevtsev, Y, Manson, L, Brooker, GA, Cumming, AD & Mullins, JJ 1995, 'A genetic model of malignant phase hypertension in rats', Kidney International, vol. 47, no. 2, pp. 529-35. https://doi.org/10.1038/ki.1995.66

    A genetic model of malignant phase hypertension in rats. / Whitworth, Caroline E.; Fleming, Stewart; Kotelevtsev, Yuri; Manson, Lynn; Brooker, Gillian A.; Cumming, Allan D.; Mullins, John J.

    In: Kidney International, Vol. 47, No. 2, 1995, p. 529-35.

    Research output: Contribution to journalArticle

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    AU - Whitworth, Caroline E.

    AU - Fleming, Stewart

    AU - Kotelevtsev, Yuri

    AU - Manson, Lynn

    AU - Brooker, Gillian A.

    AU - Cumming, Allan D.

    AU - Mullins, John J.

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    N2 - A genetic model of malignant phase hypertension in rats is described which closely parallels the natural history of untreated human malignant phase hypertension. Although the factors initiating transition from essential hypertension to the accelerated phase in humans remain unknown, we report the characteristics of a genetically determined and reproducible phenotype which was found to result from a cross between hypertensive transgenic Ren-2 rats and normotensive Sprague-Dawley (Edinburgh) rats. Male F1 hybrids developed malignant phase hypertension with a penetrance of 73.5% (95% confidence limits 65.7 to 81.3%) by 100 days of age. Phenotypic features included an accelerated rise in blood pressure, fibrinoid necrosis, activation of the renal renin-angiotensin system and microangiopathic hemolytic anemia. In an analytical cross no significant difference in blood pressure was observed between malignant phase and non-malignant phase animals prior to transition, implying that a factor in addition to hypertension appears necessary for inducing transition to the malignant phase phenotype. Segregation of the malignant phenotype suggested that susceptibility is determined by at most two genetic loci.

    AB - A genetic model of malignant phase hypertension in rats is described which closely parallels the natural history of untreated human malignant phase hypertension. Although the factors initiating transition from essential hypertension to the accelerated phase in humans remain unknown, we report the characteristics of a genetically determined and reproducible phenotype which was found to result from a cross between hypertensive transgenic Ren-2 rats and normotensive Sprague-Dawley (Edinburgh) rats. Male F1 hybrids developed malignant phase hypertension with a penetrance of 73.5% (95% confidence limits 65.7 to 81.3%) by 100 days of age. Phenotypic features included an accelerated rise in blood pressure, fibrinoid necrosis, activation of the renal renin-angiotensin system and microangiopathic hemolytic anemia. In an analytical cross no significant difference in blood pressure was observed between malignant phase and non-malignant phase animals prior to transition, implying that a factor in addition to hypertension appears necessary for inducing transition to the malignant phase phenotype. Segregation of the malignant phenotype suggested that susceptibility is determined by at most two genetic loci.

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    Whitworth CE, Fleming S, Kotelevtsev Y, Manson L, Brooker GA, Cumming AD et al. A genetic model of malignant phase hypertension in rats. Kidney International. 1995;47(2):529-35. https://doi.org/10.1038/ki.1995.66