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
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+.