Chronic potassium depletion induces renal injury, salt sensitivity, and hypertension in young rats

Background. Chronic hypokalemia has been associated with renal hypertrophy, interstitial disease, and hypertension in both adult animals and humans. H owever, the effects of potassium (K+) depletion on the rapidly growing infa nt have not been well studied. The purpose of this study was to determine t he effects of severe chronic dietary K+ depletion on blood pressure (BP) an d renal structural changes in young rats. Methods. Sprague-Dawley rats (50 +/- 5 g) were fed either a control ol a po tassium-deficient diet (<0.050% K+) for 14 to 21 days. At the end of this p eriod, the blood pressure (BP) was measured in all rats, and six rats in ea ch group were sacrificed to determine changes in renal histology and renin- angiotensin system (RAS) activity. The remaining rats in each group were th en switched to a high-salt (6% NaCl)-normal-K+ (0.536) diet or were continu ed on their respective control or K+-deficient diet for an additional sis d ays. Blood pressure measurements were done every three days until the end o f the study. Results. K+-depleted animals had significant growth retardation and increas ed RAS activity. manifested by: high plasma lenin activity, recruitment of renin-producing cells along the afferent arterioles, and down-regulation of angiotensin II receptors in renal glomeruli and ascending vasa rectae. K+- depleted kidneys also showed tubulointerstitial injury with tubular cell pr oliferation, osteopontin expression, macrophage infiltration, and early fib rosis. At week 2, K+-depleted rats had higher systolic BP than control rats . Switching to a high-salt (6%; NaCl)-normal-K+ diet resulted in further el evation of systolic BP in K+-depleted rats, which persisted even after the serum K+ was normalized. Conclusion. Dietary potassium deficiency per se increases the BP in young r ats and induces salt sensitivity that may involve at least two different pa thogenic pathways: increased RAS activity and induction of tubulointerstiti al injury.