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

doi:10.1038/ki.1995.66

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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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 language	English
Pages (from-to)	529-35
Number of pages	7
Journal	Kidney International
Volume	47
Issue number	2
DOIs	https://doi.org/10.1038/ki.1995.66
Publication status	Published - 1995

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10.1038/ki.1995.66

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title = "A genetic model of malignant phase hypertension in rats",

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.",

author = "Whitworth, {Caroline E.} and Stewart Fleming and Yuri Kotelevtsev and Lynn Manson and Brooker, {Gillian A.} and Cumming, {Allan D.} and Mullins, {John J.}",

year = "1995",

doi = "10.1038/ki.1995.66",

language = "English",

volume = "47",

pages = "529--35",

journal = "Kidney International",

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TY - JOUR

T1 - A genetic model of malignant phase hypertension in rats

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.

PY - 1995

Y1 - 1995

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.

U2 - 10.1038/ki.1995.66

DO - 10.1038/ki.1995.66

M3 - Article

C2 - 7723238

SN - 0085-2538

VL - 47

SP - 529

EP - 535

JO - Kidney International

JF - Kidney International

IS - 2

ER -

A genetic model of malignant phase hypertension in rats

Abstract

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