Exaggerated response to restraint stress in rats congenic for the chromosome 1 blood pressure quantitative trait locus.

摘要

1. To understand the roles of a putative hypertension gene in the chromosome 1 quantitative trait locus (QTL) region, the response to restraint stress was studied in strains congenic for this QTL. 2. To establish congenic strains, the QTL region was introgressed from stroke-prone spontaneously hypertensive rats (SHRSP)/Izm to Wistar-Kyoto/Izm (WKY/Izm) rats by repeated backcrossing. Two congenic strains (WKYpch1.0 and WKYpch1.1) were established to cover the whole QTL region between D1Wox29 and D1Arb21 (approximately 40 cM) and a smaller region between D1Smu11 and D1Arb21 (approximately 10 cM), respectively. After telemetry probes were implanted, rats were exposed to restraint stress to investigate the blood pressure response. 3. Basal blood pressure measured by radiotelemetry differed significantly between WKY rats and WKYpch1.0 (103 +/- 10 and 116 +/- 4 mmHg, respectively; P = 0.002 by anova). When exposed to restraint stress, WKYpch1.0 showed a greater increase in blood pressre than did WKY rats. The exaggerated response in the WKYpch1.0 strain was abolished by chemical sympathectomy using guanethidine. The WKYpch1.1 rats did not differ significantly from WKY rats either in basal blood pressure or in the response to restraint stress. 4. In conclusion, a QTL for high blood pressure was successfully introgressed in the established congenic strain, WKYpch1.0. A gene (or genes) in the chromosome 1 QTL region modulates the cardiovascular responses to restraint stress in these congenic rats, probably through the sympathetic nervous system.