Alemayehu, Adamu, Laura Breen, and Morton P. Printz. A new inbred Wistar-Kyoto rat substrain exhibiting apparent salt sensitivity and borderline hypertension. Am J Physiol Heart Circ Physiol 283: H1181-H1190, 2002. First published May 23, 2002 10.1152/ajpheart.00187.2002The normotensive Wistar-Kyoto (WKY) rat strain is a traditional control for the spontaneously hypertensive rat (SHR). We found trait differences between two inbred normotensive WKY strains, derived originally from different vendors, and compared these two strains from La Jolla-Taconic Farms (WKY/lj-tf) and La Jolla-Charles River (WKY/lj-cr) with the inbred SHR/lj-cr for cardiovascular, diurnal, and activity traits under normal and high (8%) NaCl diets. Marked genetic diversity was found between the two vendor-derived WKY. By using an extended study design and radiotelemetry, we compared WKY/lj-cr, WKY/lj-tf, and SHR/lj-cr with the following results: systolic pressure (120 Ϯ 1, 133 Ϯ 1, 168 Ϯ 3 mmHg, respectively); diurnal variation in heart rate (⌬HR: 46 Ϯ 3, 71 Ϯ 4, 57 Ϯ 2 beats/min, respectively); and salt sensitivity of arterial pressure (⌬systolic: 10 Ϯ 1, 21 Ϯ 1, 20 Ϯ 1 mmHg, respectively). The WKY/lj-tf genotype apparently results in compromised control of arterial pressure and heart rate, especially during high NaCl intake, and greater susceptibility to high pressure (i.e., high NaCl-induced secondary changes). WKY/lj-tf thus constitutes a new inbred borderline hypertensive WKY substrain offering unique opportunities for genomic studies into the development of genetic hypertension. inbred strains; hypertension sodium-dependent; genotype; circadian rhythm; radiotelemetry; heart rate; polymorphism MOST INVESTIGATORS have been using descendants of the normotensive Wistar-Kyoto (WKY) rat strain as the control for the Okamoto and Aoki (20) spontaneously hypertensive rat (SHR). As a result of both highly inbred original stock and standardized breeding practices, virtual uniformity has resulted in the SHR supplied by major commercial vendors (5). However, the rigorous procedures applied to the initial inbreeding and subsequent distribution of the SHR were not used for the WKY rat derived after the SHR. As a result, animals were distributed to commercial suppliers as early as the 10th generation of inbreeding (13). Furthermore, subsequent breeding was not standardized with some suppliers (including Charles River Laboratories) maintaining brother-sister matings (10) to sustain the founder stock, whereas others (including Taconic Farms) used a random breeding (outbred) protocol (26).Studies from several laboratories, including our own, compared WKY rats from Charles River Laboratories (WKY/cr; Wilmington, MA) and Taconic Farms (WKY/ tf; Germantown, NY) and reported pronounced trait differences (9,13,14,24). Our own laboratory (8), as early as 1984, noted differences in 1) consummatory behaviors including an enhanced salt preference in WKY/tf, 2) age-weight relationships, and 3) cardiovascular traits between these WKY substrains. Furthermore, we rep...