A 1.8-Mbp fragment on chromosome 1 affects sympathetic response to stress: evaluation in reciprocal congenic strains between stroke-prone spontaneously hypertensive rat and Wistar-Kyoto rat.
BACKGROUND
In the previous studies, we indicated that a gene (or genes) responsible for exaggerated sympathetic response to stress was located in a chromosome 1 QTL for blood pressure (BP) in stroke-prone spontaneously hypertensive rat (SHRSP). In this study, we narrowed down the candidate region to a 1.8-Mbp fragment between D1Rat171 and D1Wox33, and established reciprocal congenic strains for this region.


METHODS
Reciprocal congenic strains were established by introgressing the chromosomal segment from SHRSP/Izm into WKY/Izm (Wpch1.21) and vice versa (SPwch1.72). The urinary norepinephrine excretion (u-NE) was quantified with high-performance liquid chromatography in the urine collected under 6 h of cold stress (4°C). ECG was recorded using the telemetry under 3 h of restraint stress, and the relative sympathetic activity was evaluated as the low frequency/high frequency ratio by the power spectral analysis. BP under the stresses was evaluated by the telemetry.


RESULTS
The increases in the u-NE during the cold stress and in the low frequency/high frequency ratio under the restraint stress were significantly greater in Wpch1.21 when compared with Wistar-Kyoto (WKY) rat. The increases in BP both under the cold and the restraint stresses were significantly greater in Wpch1.21 than in WKY. In the reciprocal congenic strain, SPwch1.72, the effects of the transferred fragment on the sympathetic stress responses were confirmed as lower u-NE and low frequency/high frequency in this strain than in SHRSP. Further, the BP responses both to the cold and the restraint stresses were significantly greater in SHRSP than in SPwch1.72.


CONCLUSIONS
These results indicated that a small fragment on chromosome 1 harbored a gene (or genes) influencing the sympathetic response to different stresses.
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Bing
B
Xiao
Yuji
Y
Harada
Kohei
K
Kawakami
Toru
T
Nabika
D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D003080:Cold Temperature / Q000009:adverse effects; D004562:Electrocardiography; D006339:Heart Rate / Q000235:genetics; D008297:Male; D009638:Norepinephrine / Q000652:urine; D040641:Quantitative Trait Loci; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D011921:Rats, Inbred WKY / Q000235:genetics; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000235:genetics*; D013564:Sympathetic Nervous System / Q000502:physiology*
D009638:Norepinephrine