This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Negrín, C. D. Articles by Dominiczak, A. F. Search for Related Content PubMed PubMed Citation Articles by Negrín, C. D. Articles by Dominiczak, A. F. Related Collections Cerebrovascular disease/stroke Animal models of human disease Genetics of Stroke Genetics of cardiovascular disease

(Hypertension. 2001;37:391.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Reciprocal Consomic Strains to Evaluate Y Chromosome Effects

Cervantes D. Negrín; Martin W. McBride; Hillary V. O. Carswell; Delyth Graham; Fiona J. Carr; James S. Clark; Baxter Jeffs; Niall H. Anderson; I. Mhairi Macrae; Anna F. Dominiczak

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.WKYGlaY_w (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.SPGlaY_s (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.SPGlaY_s (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.WKYGlaY_w (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, N. N. Huynh, C. A. Hamilton, E. Beattie, R. A.J. Smith, H. M. Cocheme, M. P. Murphy, and A. F. Dominiczak Mitochondria-Targeted Antioxidant MitoQ10 Improves Endothelial Function and Attenuates Cardiac Hypertrophy Hypertension, August 1, 2009; 54(2): 322 - 328. [Abstract] [Full Text] [PDF]

				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]