Kidney specificity of rat chromosome 1 blood pressure quantitative trait locus region.
Rat chromosome 1 has a region containing loci that influence blood pressure. In the present study, we investigated whether these loci mediate their effect via the kidney. Taking advantage of the histocompatibility between a congenic strain (WKY.SHR-Sa, which contains the relevant chromosomal region from the spontaneously hypertensive rat) and its parental strain, the Wistar-Kyoto rat (WKY), we compared the effect of transplanting a kidney at 5 to 6 weeks of age from either congenic rats or WKY into bilaterally nephrectomized WKY. WKY.SHR-Sa animals and WKY with intact kidneys and with unilateral nephrectomy were studied as controls. Blood pressure was measured at 12, 16, 20, and 25 weeks of age. At all time points, blood pressure was significantly higher (by between 8 to 22 mm Hg, P<0.001) in 2-kidney WKY.SHR-Sa animals compared with WKY. This genotype-related difference was maintained in unilaterally nephrectomized rats. Most importantly, WKY that received transplants from WKY.SHR-Sa rats had significantly higher blood pressure (P<0.001 at all time points) compared with those that received transplants from other WKY. At any age, this difference was between 70% to 100% of the difference observed between the 1-kidney groups. There was no difference in plasma urea or creatinine between groups or evidence of chronic rejection in the cross-transplant group. The findings indicate that the major proportion of the blood pressure effect of loci on rat chromosome 1 is mediated through the kidney, and provide a rational basis for investigating genes located in the relevant chromosomal region and expressed in the kidney as likely candidates.
Clemitson
Jenny-Rebecca
JR
Department of Cardiology, University of Leicester, Leicester, United Kingdom.
Pratt
Julian R
JR
Frantz
Simon
S
Sacks
Steven
S
Samani
Nilesh J
NJ
D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics*; D001835:Body Weight; D002875:Chromosomes; D003404:Creatinine / Q000097:blood; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000235:genetics*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D007700:Kinetics; D009929:Organ Size; D019655:Quantitative Trait, Heritable; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014508:Urea / Q000097:blood
D014508:Urea; D003404:Creatinine