Interaction between chromosome 2 and 3 regulates pulse pressure in the stroke-prone spontaneously hypertensive rat

Koh-Tan, H.H. C., McBride, M. W. , McClure, J. D. , Beattie, E., Young, B., Dominiczak, A. F. and Graham, D. (2013) Interaction between chromosome 2 and 3 regulates pulse pressure in the stroke-prone spontaneously hypertensive rat. Hypertension, 62(1), pp. 33-40. (doi:10.1161/HYPERTENSIONAHA.111.00814)

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Abstract

In an F2 cross between stroke-prone spontaneously hypertensive (SHRSP) and Wistar Kyoto (WKY) rats, we previously identified blood pressure quantitative trait loci (QTL) on rat chromosome (RNO) 2 and a pulse pressure QTL on RNO3. The aims of this study were to confirm the QTL on RNO3 and to investigate interaction between RNO2 and RNO3 loci through the generation and phenotypic assessment of single RNO3 congenic (SP.WKYGla3a) and bicongenic (SP.WKYGla2a/3a) strains. Hemodynamic profiling, vascular function, and renal histology were examined in these newly generated strains along with the previously reported RNO2 congenic strain (SP.WKYGla2a). Our results demonstrate significant equivalent reduction in systolic, diastolic, and pulse pressure phenotypes in SP.WKYGla3a and SP.WKYGla2a rats, whereas greater reductions were observed with the SP.WKYGla2a/3a bicongenic strain achieving blood pressure levels similar to normotensive WKY rats. Epistasis was observed between pulse pressure QTL on RNO2 and 3 at baseline and during 1% salt challenge. Vascular function and renal pathology studies indicate that QTL on RNO3 are responsible for salt-induced kidney pathology, whereas QTL on RNO2 seem to have greater impact on vascular function. RNO3 congenic and bicongenic strains have confirmed the importance of SHRSP alleles in the RNO3 congenic interval on pulse pressure variability and end-organ damage. These strains will allow interrogation of complex gene–gene and gene–environment interactions contributing to salt-sensitive hypertension and renal pathology in the SHRSP rat.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Young, Dr Barbara and Graham, Dr Delyth and McBride, Dr Martin and Dominiczak, Professor Anna and Beattie, Mrs Elisabeth and Koh-Tan, Dr Han Hui and McClure, Dr John
Authors: Koh-Tan, H.H. C., McBride, M. W., McClure, J. D., Beattie, E., Young, B., Dominiczak, A. F., and Graham, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Hypertension
Publisher:American Heart Association
ISSN:0194-911X
ISSN (Online):1524-4563
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
2393330BHF ChairAnna DominiczakBritish Heart Foundation (BHF)CH/98001/10285RI CARDIOVASCULAR & MEDICAL SCIENCES
464051Genomics and proteomics of hypertension and its vascular complications: the pathwayomic strategies.Anna DominiczakBritish Heart Foundation (BHF)RG/07/005/23633RI CARDIOVASCULAR & MEDICAL SCIENCES
302341Cardiovascular Functional genomics - Translating experimental work to human diseaseAnna DominiczakWellcome Trust (WELLCOME)066780/Z/01/ZRI CARDIOVASCULAR & MEDICAL SCIENCES