RRC ID 2803
Author Yao H, Cui ZH, Masuda J, Nabika T.
Title Congenic removal of a QTL for blood pressure attenuates infarct size produced by middle cerebral artery occlusion in hypertensive rats.
Journal Physiol. Genomics
Abstract A genome-wide screen found a blood pressure quantitative trait locus (QTL) on rat chromosome 1 in stroke-prone spontaneously hypertensive rats of a Japanese colony (SHRSP/Izm). In the present study, we investigated the effects of congenic removal of this QTL from SHRSP/Izm on infarct size produced by middle cerebral artery (MCA) occlusion. To establish the congenic strain (SHRSPwch1.0), the blood pressure QTL was introgressed from Wistar-Kyoto (WKY)/Izm to SHRSP/Izm by repeated backcrossing. Male SHRSP/Izm [10-12 wk old (young adult) n = 8, 5 mo old (adult) n = 17] and SHRSPwch1.0 (young adult n = 7, adult n = 15) were randomly assigned to distal MCA occlusion. Resting mean arterial blood pressure (MABP) was 212 +/- 23 mmHg in adult SHRSPwch1.0, which was significantly lower than 241 +/- 22 mmHg in SHRSP/Izm. Infarct volume in the congenic rats was significantly decreased compared with that in SHRSP/Izm (66.4 +/- 21.5 mm(3) vs. 103.4 +/- 24.8 mm(3)). Cerebral blood flow (CBF), determined at collaterally-perfused cortex with laser-Doppler flowmetry after MCA occlusion, was significantly greater in adult SHRSPwch1.0 compared with CBF in adult SHRSP/Izm. In young adult rats, there were no significant differences in MABP or in infarct volume between SHRSPwch1.0 and SHRSP/Izm. The congenic removal of a blood pressure QTL lowered blood pressure and caused a substantial reduction in infarct volume (-36%) with increased collateral CBF after MCA occlusion in the congenic rat. We demonstrated for the first time that the congenic strategy is useful to investigate the effects of genetic hypertension on focal ischemia or stroke.
Volume 30(1)
Pages 69-73
Published 2007-6-19
DOI 10.1152/physiolgenomics.00149.2006
PII 00149.2006
PMID 17327494
MeSH Animals Animals, Congenic Arterial Occlusive Diseases / complications Blood Pressure / genetics* Blood Pressure / physiology Cerebral Arteries / pathology Cerebral Arteries / physiopathology* Cerebrovascular Circulation Chromosomes, Mammalian / genetics Female Hypertension / genetics Hypertension / physiopathology Infarction, Middle Cerebral Artery / etiology Infarction, Middle Cerebral Artery / genetics* Infarction, Middle Cerebral Artery / pathology Laser-Doppler Flowmetry Male Quantitative Trait Loci / genetics* Random Allocation Rats Rats, Inbred SHR Rats, Inbred WKY
IF 2.581
Times Cited 14
Rats SHRSP.WKY-(D1Wox29-D1Arb21)/Izm(strainID=480)