Abstract 2732: Interacting Blood Pressure Loci in the Stroke-Prone Spontaneously Hypertensive Rat.
Background: In a previous genome wide linkage study we identified blood pressure quantitative trait loci (QTL) mapping to rat chromosome 2 and chromosome 3 in an F2 cross derived from SHRSP and WKY strains. We also identified a significant interaction between loci on chromosomes 2 and 3 using Pseudomarker (v 0.9) statistical framework. The aim of this study was to generate a double congenic strain to confirm chromosome 3 QTL and investigate the interaction between loci on the implicated chromosomes.
Methods: A marker-assisted breeding strategy was used to generate the SP.WKYGla2a/3a double congenic strain (D2Rat13-D2Rat157, D3Mgh16-D3Wox28), using SHRSP as recipient and WKY as the donor strain. Haemodynamic measurements were carried out using radiotelemetry over a 5-week baseline period followed by 3 weeks of salt-loading (1%).
Results: Radiotelemetry data for systolic blood pressure and pulse pressure are illustrated in figure⇓ a + b respectively. Systolic blood pressure was significantly reduced in the SP.WKYGa2a/3a strain (n=7) compared to SHRSP (n=13) (p = 0.0001, F = 97.77, repeated measures ANOVA). Pulse pressure was also significantly reduced compared to SHRSP (p=0.0001, F=34.17) and achieved levels comparable to WKY (n=10). Pulse pressure diurnal variation observed in SHRSP during salt-loading was abolished in the double congenic strain (AUC; p=0.0001, F=13.56).
Conclusions: Almost complete reversal of SHRSP hypertensive haemodynamic profiles has been achieved in the SP.WKYGla2a/3a double congenic strain. This strain will allow interrogation of complex gene-gene, gene-environment interactions contributing to salt-sensitive hypertension in the SHRSP.