Hypokalemia induces renal injury and alterations in vasoactive mediators that favor salt sensitivity

Citation
Si. Suga et al., Hypokalemia induces renal injury and alterations in vasoactive mediators that favor salt sensitivity, AM J P-REN, 281(4), 2001, pp. F620-F629
Citations number
50
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
ISSN journal
03636127 → ACNP
Volume
281
Issue
4
Year of publication
2001
Pages
F620 - F629
Database
ISI
SICI code
0363-6127(200110)281:4<F620:HIRIAA>2.0.ZU;2-H
Abstract
We investigated the hypothesis that hypokalemia might induce renal injury v ia a mechanism that involves subtle renal injury and alterations in local v asoactive mediators that would favor sodium retention. To test this hypothe sis, we conducted studies in rats with diet-induced K+ deficiency. We also determined whether rats with hypokalemic nephropathy show salt sensitivity. Twelve weeks of hypokalemia resulted in a decrease in creatinine clearance , tubulointerstitial injury with macrophage infiltration, interstitial coll agen type III deposition, and an increase in osteopontin expression (a tubu lar marker of injury). The renal injury was greatest in the outer medulla w ith radiation into the cortex, suggestive of an ischemic etiology. Consiste nt with this hypothesis, we found an increased uptake of a hypoxia marker, pimonidazole, in the cortex. The intrarenal injury was associated with incr eased cortical angiontensin-converting enzyme (ACE) expression and continue d cortical angiotensin II generation despite systemic suppression of the re nin-angiotensin system, an increase in renal endothelin-1, a decrease in re nal kallikrein, and a decrease in urinary nitrite/nitrates and prostaglandi n E-2 excretion. At 12 wk, hypokalemic rats were placed on a normal-K+ diet with either high (4%)- or low (0.01%)-NaCl content. Despite correction of hypokalemia and normalization of renal function, previously hypokalemic rat s showed an elevated blood pressure in response to a high-salt diet compare d with normokalemic controls. Hypokalemia is associated with alterations in vasoactive mediators that favor intrarenal vasoconstriction and an ischemi c pattern of renal injury. These alterations may predispose the animals to salt-sensitive hypertension that manifests despite normalization of the ser um K+.