Exaggerated response to cold stress in a congenic strain for the quantitative trait locus for blood pressure

Stroke-prone spontaneously hypertensive rats (SHRSP) are known to have sympathetic hyperactivity to various stimuli. In the search for 'intermediate phenotypes' inferring the function of hypertension genes, the present study assessed responsiveness to cold stress in a congenic strain derived from SHRSP/Izm and Wistar-Kyoto/Izm (WKY/Izm).

A congenic strain, WKYpch1.0, was established by 10 generations of backcrossing to transfer the chromosomal fragment between D1Wox29 and D1Arb21 of SHRSP to WKY. This fragment covered the 100:1 confidence interval of the quantitative trait locus (QTL) for blood pressure identified in a previous study. Response to cold stress was studied by exposing rats to 4 degrees C for 4 h. Blood pressure was monitored with telemetry. Urine was collected during the exposure, and urinary concentrations of catecholamines were measured by high-performance liquid chromatography.

Under the cold stress, urinary excretion of norepinephrine (NE) and vanillylmandelic acid (VMA), as well as the plasma level of NE, was significantly greater in WKYpch1.0 than in WKY. The increase in blood pressure during the cold stress was also greater in WKYpch1.0 than in WKY. Further, neonatal chemical sympathectomy using guanethidine abolished the exaggerated response in blood pressure and in urinary excretion of NE and VMA in WKYpch1.0.

These results suggested that the QTL region on rat chromosome 1 harbored genes responsible for the exaggerated response of the sympathetic nervous system to the cold stress. The relationship of this with the pathogenesis of hypertension should be elucidated in future studies.