Reciprocal consomic strains to evaluate Y chromosome effects

We have previously demonstrated that the SHRSP Y chromosome contains a locu s that contributes to hypertension in SHRSP/WKY F2 hybrids and that SHRSP e xhibit an increased vulnerability to focal cerebral ischemia after permanen t middle cerebral artery occlusion (MCAO). This increased vulnerability is inherited as a codominant trait, and a putative role for the Y chromosome h as been suggested in Fl hybrids. The objective of this study was to investi gate further the role of Y chromosome in blood pressure (BP) regulation and in the vulnerability to cerebral ischemia, We have constructed consomic st rains by selectively replacing the Y chromosome from WKY rats with that of SHRSP, and vice versa, by using a marker-assisted breeding strategy. Perman ent MCAO was carried out by electrocoagulation, with infarct volume express ed as a percentage of the ipsilateral hemisphere. Systolic blood pressure w as 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 pe riod. In the reciprocal consomic strain, WKY.SPGlaY(s) (n=5), systolic BP w as increased compared with WKY parental strain (n=6) (147.6+/-2.4 mm Hg ver sus 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 pa rental 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 t hat the SHRSP Y chromosome harbors a locus contributing to systolic BP, whe reas no contribution to vulnerability to cerebral ischemia can be detected.