(Hypertension. 2001;37:391.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Reciprocal Consomic Strains to Evaluate Y Chromosome Effects
From the Department of Medicine and Therapeutics (C.D.N., M.W.M., D.G., F.J.C., J.S.C., N.H.A., A.F.), University of Glasgow, Western Infirmary, and Wellcome Surgical Institute University of Glasgow (H.V.O.C.; I.M.M.), Glasgow, United Kingdom; and Endocrinology, Metabolism and Medicine, Northwestern University Medical School (B.J.), Chicago, Ill.
Correspondence to Prof Anna F. Dominiczak, Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT. E-mail anna.dominiczak{at}clinmed.gla.ac.uk
We have previously demonstrated that the SHRSP Y chromosome contains a locus that contributes to hypertension in SHRSP/WKY F2 hybrids and that SHRSP exhibit an increased vulnerability to focal cerebral ischemia after permanent middle cerebral artery occlusion (MCAO). This increased vulnerability is inherited as a codominant trait, and a putative role for the Y chromosome has been suggested in F1 hybrids. The objective of this study was to investigate further the role of Y chromosome in blood pressure (BP) regulation and in the vulnerability to cerebral ischemia. We have constructed consomic strains by selectively replacing the Y chromosome from WKY rats with that of SHRSP, and vice versa, by using a marker-assisted breeding strategy. Permanent MCAO was carried out by electrocoagulation, with infarct volume expressed as a percentage of the ipsilateral hemisphere. Systolic blood pressure was measured by radiotelemetry during a baseline period of 5 weeks followed by a 3-week period of salt loading. We observed that the transfer of the Y chromosome from WKY onto SHRSP background significantly reduced systolic BP in consomic strains, SP.WKYGlaYw (n=6) versus SHRSP (n=6) (209.2±10.4 mm Hg versus 241.7±7.7 mm Hg, F=5.88, P=0.038) during the salt-loading period. In the reciprocal consomic strain, WKY.SPGlaYs (n=5), systolic BP was increased compared with WKY parental strain (n=6) (147.6±2.4 mm Hg versus 132.6±5.1 mm Hg, F=6.11, P=0.035) during baseline. Infarct volumes in consomic strains were not significantly different from their respective parental strain: WKY.SPGlaYs (n=7) versus WKY (n=7), 22.8±3.7% versus 22.2±8.0%, 95% CI=-12.7, 4.2, P=0.3; SP.WKYGlaYw (n=7) versus SHRSP (n=6), 37.7±4.4% versus 33.6±7.6%, 95% CI=-20.3, 12.1, P=0.5. We conclude that the SHRSP Y chromosome harbors a locus contributing to systolic BP, whereas no contribution to vulnerability to cerebral ischemia can be detected.
Key Words: hypertension • stroke • genetics • SHRSP • consomics • focal cerebral ischemia • middle cerebral artery occlusion
This article has been cited by other articles:
 |
|
 |
|
  D. Graham, M. W. McBride, M. Gaasenbeek, K. Gilday, E. Beattie, W. H. Miller, J. D. McClure, J. M. Polke, A. Montezano, R. M. Touyz, et al. Candidate Genes That Determine Response to Salt in the Stroke-Prone Spontaneously Hypertensive Rat: Congenic Analysis Hypertension, December 1, 2007; 50(6): 1134 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Prows, A. P. Hafertepen, W. J. Gibbons Jr., A. V. Winterberg, and T. G. Nick A genetic mouse model to investigate hyperoxic acute lung injury survival Physiol Genomics, August 20, 2007; 30(3): 262 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. McBride, F. J. Charchar, D. Graham, W. H. Miller, P. Strahorn, F. J. Carr, and A. F. Dominiczak Functional genomics in rodent models of hypertension J. Physiol., January 1, 2004; 554(1): 56 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Charchar, M. Tomaszewski, S. Padmanabhan, B. Lacka, M. N. Upton, G. C. Inglis, N. H. Anderson, A. McConnachie, E. Zukowska-Szczechowska, W. Grzeszczak, et al. The Y Chromosome Effect on Blood Pressure in Two European Populations Hypertension, February 1, 2002; 39(2): 353 - 356. [Abstract] [Full Text] [PDF]
|
|