DEVELOPMENT, GENOTYPE AND PHENOTYPE OF A NEW COLONY OF THE SABRA HYPERTENSION PRONE (SBH Y) AND RESISTANT (SBN/Y) RAT MODEL OF SALT SENSITIVITY AND RESISTANCE/

Objectives Variations in the blood pressure response to salt-loading, the lack of quality control measures, and the need to prepare the stra ins for genetic studies led to renewed secondary inbreeding of the ori ginal colony of Sabra hypertension prone (SBH) and resistant (SBN) rat s in order to regain genotypic and phenotypic homogeneity of the subst rains. Methods Animals from the original breeding colony were selectiv ely inbred for basal normotension and for susceptibility or resistance to the development of hypertension following salt-loading with deoxyc orticosterone acetate (DOCA)-salt. Efficacy of inbreeding was tested b y genome screening with 416 microsatellite primer sets, Phenotyping wa s based on measurements of systolic blood pressure by the tail-cuff me thodology in awake, undisturbed animals maintained on standard diet an d after salt-loading with DOCA-salt, Telemetric measurements of blood pressure were performed in a small number of animals to validate tail- cuff measurements. Results Animals from the new colony were designated SBH/y and SBN/y to differentiate from the original colony, Fourteen g enerations have been inbred over the past 4 years, Of the 402 microsat ellites that amplified, 183 (45.5%) were polymorphic between the two s ubstrains, and not a single locus was found to be heterozygous in eith er substrain, Phenotypic characteristics are provided for SBH/y and SB N/y rats with respect to tail-cuff systolic blood pressure, The values obtained, which were validated by telemetry, demonstrate classical fe atures of salt sensitivity or resistance, respectively. Conclusions Th e genetic homogeneity found in SBH/y and SBN/y, the phenotype demonstr ating salt-sensitivity or salt-resistance in terms of development of h ypertension, and the relatively high frequency of informative genetic markers identify this Sabra rat model as highly suited for studies con cerning the molecular genetics of gene-environment interactions affect ing blood pressure regulation.