Reciprocal consomic strains to evaluate Y chromosome effects

被引:30
作者
Negrín, CD
McBride, MW
Carswell, HVO
Graham, D
Carr, FJ
Clark, JS
Jeffs, B
Anderson, NH
Macrae, IM
Dominiczak, AF [1 ]
机构
[1] Univ Glasgow, Western Infirm, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland
[2] Univ Glasgow, Wellcome Surg Inst, Glasgow, Lanark, Scotland
[3] Northwestern Univ, Sch Med, Chicago, IL USA
关键词
hypertension; stroke; genetics; SHRSP; consomics; focal cerebral ischemia; middle cerebral artery occlusion;
D O I
10.1161/01.HYP.37.2.391
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 Fl 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.
引用
收藏
页码:391 / 397
页数:7
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