Genetic Characterization of the 'New' Harlan Sprague Dawley Dahl Salt-Sensitive Rats

In 1994, it was reported that Dahl salt-sensitive SS/Jr rats supplied by Harlan Sprague Dawley were genetically contaminated and resistant to the pressor effects of a high salt diet. Harlan Sprague Dawley subsequently developed new pedigree expansion and production colonies from their foundation colony to supply new, purportedly inbred, Harlan Sprague Dawley SS/Jr (S). To evaluate the genetic integrity and salt sensitivity of these new S, we performed genotyping (microsatellite DNA markers) and phenotyping (radiotelemetric arterial pressure) of 12 S, 16 "authentic" SS/Jr from the inbred colony of John Rapp (S), 9 Harlan Sprague Dawley salt-resistant SR/Jr (R ()), and (genotyping only) 6 known "contaminated" Harlan Sprague Dawley Dahl SS/Jr (S sup *). In the genotyping studies, 20 of 22 markers revealed polymorphisms between S and S sup * and 18 were polymorphic between S and R, but none of the 22 markers revealed polymorphisms between S and the new S. The phenotyping studies showed that during an ultra-low salt diet, mean arterial pressure was higher (P < .05) in both authentic S (129 plus/minus 2 mm Hg; mean plus/minus SE) and new S (120 plus/minus 2 mm Hg) than in R (93 plus/minus 1 mm Hg). A high salt diet increased mean arterial pressure in every S and S. Increases in mean arterial pressure after 4 weeks of a high salt diet were significantly (P < .05) greater in authentic S (+51 plus/minus 3 mm Hg) than in new S (+39 plus/minus 3 mm Hg). In addition, salt-induced mortality was significantly greater in S (62.5%) than S (8.3%) after 8 weeks (P < .01). S were genotypically indistinguishable from S, had an elevated arterial pressure on a low salt diet, and had a pressor response to salt. Thus, the new S supplied to us had several characteristics of inbred Dahl SS/Jr and did not have evidence of the previously detected genetic contamination. However, phenotypic characteristics such as body weight, salt-induced hypertension, and mortality were significantly different in S compared with S. This may reflect genetic differences between these two strains or differences in environmental factors and suggests that the S and S may now constitute distinct substrains of Dahl SS/Jr. (Hypertension. 1996;27[part 2]:546-551.)