Reciprocal consomic strains to evaluate Y chromosome effects

Negrin, C., McBride, M. , Carswell, H., Graham, D., Carr, F., Clark, J., Jeffs, B., Anderson, N., Macrae, I. and Dominiczak, A. (2001) Reciprocal consomic strains to evaluate Y chromosome effects. Hypertension, 37, pp. 391-397. (doi: 10.1161/01.HYP.37.2.391)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Clark, Dr John and Macrae, Professor Mhairi and Carswell, Dr Hilary and McBride, Dr Martin and Dominiczak, Professor Anna
• Authors: Negrin, C., McBride, M., Carswell, H., Graham, D., Carr, F., Clark, J., Jeffs, B., Anderson, N., Macrae, I., and Dominiczak, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
• Journal Name: Hypertension
• Publisher: American Heart Association
• ISSN: 0194-911X