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(Hypertension. 1996;27:546-551.)
© 1996 American Heart Association, Inc.

Articles

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

Roxanne Y. Walder¹; Donald A. Morgan¹; William G. Haynes¹; Rita D. Sigmund; Ann M. McClain; John B. Stokes; Allyn L. Mark

From the Hypertension Specialized Center of Research, The Cardiovascular Center and Department of Internal Medicine, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City.

Abstract 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^HSD). To evaluate the genetic integrity and salt sensitivity of these new S^HSD, we performed genotyping (microsatellite DNA markers) and phenotyping (radiotelemetric arterial pressure) of 12 S^HSD, 16 "authentic" SS/Jr from the inbred colony of John Rapp (S^Rapp), 9 Harlan Sprague Dawley salt-resistant SR/Jr (R^HSD), and (genotyping only) 6 known "contaminated" Harlan Sprague Dawley Dahl SS/Jr (S*). In the genotyping studies, 20 of 22 markers revealed polymorphisms between S^Rapp and S* and 18 were polymorphic between S^Rapp and R^Rapp, but none of the 22 markers revealed polymorphisms between S^Rapp and the new S^HSD. The phenotyping studies showed that during an ultra–low salt diet, mean arterial pressure was higher (P<.05) in both authentic S^Rapp (129±2 mm Hg; mean±SE) and new S^HSD (120±2 mm Hg) than in R^HSD (93±1 mm Hg). A high salt diet increased mean arterial pressure in every S^HSD and S^Rapp. Increases in mean arterial pressure after 4 weeks of a high salt diet were significantly (P<.05) greater in authentic S^Rapp (+51±3 mm Hg) than in new S^HSD (+39±3 mm Hg). In addition, salt-induced mortality was significantly greater in S^Rapp (62.5%) than S^HSD (8.3%) after 8 weeks (P<.01). S^HSD were genotypically indistinguishable from S^Rapp, had an elevated arterial pressure on a low salt diet, and had a pressor response to salt. Thus, the new S^HSD 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^HSD compared with S^Rapp. This may reflect genetic differences between these two strains or differences in environmental factors and suggests that the S^HSD and S^Rapp may now constitute distinct substrains of Dahl SS/Jr.

Key Words: sodium • arterial pressure • telemetry • phenotype • genotype

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