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Expression of Hypertension During Development of an Okamoto SHR/Brown Norway Congenic Rat Strain
Author(s) -
Wyatt Erin A,
Osborn Jeffrey L.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1207-b
Subject(s) - congenic , blood pressure , offspring , allele , endocrinology , medicine , mean arterial pressure , spontaneously hypertensive rat , biology , phenotype , genetics , gene , pregnancy , heart rate
The Okamoto Spontaneous Hypertensive Rat (SHR) is known to develop hypertension from a number of physiologic perturbations of the cardiovascular system including but not limited to altered neural control of blood pressure. This study documents the development of hypertension over 5 generations of breeding in a congenic strain derived from a male Brown Norway (BN) rat (mean arterial pressure = 96 mmHg) and a female SHR (mean arterial pressure = 153 mmHg). We hypothesize that alleles responsible for hypertension are derived from the original SHR and these alleles are localized onto a genomic background predominantly from the BN. Blood pressure phenotypes were determined beginning at 7 weeks of age using tail cuff plethysmography. Hypertension was defined in all rats as mean arterial pressure (MAP) exceeding 125 mmHg and normotension as MAP less than 105 mmHg. Female, F1 offspring with MAP equal to or greater than the original SHR (n = 4) were back bred to the original BN male. Subsequent offspring strains were raised to adulthood with MAP determined at 7, 10 and 14 weeks of age. At the F5 generation, hypertension has been maintained in 22% of the offspring from the original SHR/BN mating. There was no correlation of blood pressure related to gender in any of the generations. Three F6 generation litters have been produced and await complete phenotyping. These results demonstrate that dominant alleles responsible for the development of neurogenic hypertension can be localized on a genomic background that is resistant to hypertension. Future genomic analysis will determine the relationships among specific genomic sites and hypertension. (Supported by an APS Summer Undergraduate Research Fellowship to Erin Wyatt)