TY - JOUR
T1 - Reverse pharmacological effect of loop diuretics and altered rBSC1 expression in rats with lithium nephropathy
AU - Michimata, Mari
AU - Fujita, Sayuri
AU - Araki, Tsutomu
AU - Mizukami, Kazuhiko
AU - Kazama, Itsuro
AU - Muramatsu, Yasuko
AU - Suzuki, Michiko
AU - Kimura, Tokihisa
AU - Sasaki, Sei
AU - Imai, Yutaka
AU - Matsubara, Mitsunobu
N1 - Funding Information:
This work was supported by Research Grants for Scientific Research (01180, 12877163, 13470085, 13671095 and 10470102) from the Ministry of Science and Education. We thank Ms. Kiyomi Kisu for her excellent technical assistance, and Ms. Hiroko Ikeda, Ms. Noriko Takano, and Miss Akiko Kohinata for their secretarial assistance.
PY - 2003
Y1 - 2003
N2 - Background. Renal urinary concentration is associated with enhanced expression of rBSC1, a rat sodium cotransporter, in the thick ascending limb of Henle. Increased expression of rBSC1 was reported recently in nephrogenic diabetes insipidus induced by lithium chloride (Li nephropathy). However, the pathophysiological implication of altered rBSC1 expression has not yet been investigated. Methods. Li nephropathy was induced in rats by an oral administration of 40 mmol lithium/kg dry food. In rats with reduced urinary osmolality to less than 300 mOsm/kg H2O, we examined the expression of rBSC1 mRNA and protein, plasma arginine vasopressin (AVP) and RNA expression of kidney-specific water channel, aquaporin-2 (AQP2), of collecting ducts. Rats with Li nephropathy were treated with furosemide (3 mg/kg body weight), which blocks the activity of rBSC1, and changes in urine concentration, plasma AVP, medullary accumulation of Li ions, and apical AQP2 expression were determined. Results. Rats with Li nephropathy showed increased rBSC1 RNA and protein expression and reduced AQP2 RNA. In these rats, furosemide, which induces dilution of urine and polyuria in normal rats, resulted in a progressive and significant rise in urine osmolality from 167 ± 11 (mean ± SD) at baseline to 450 ± 45 mOsm/kg H2O at three hours after administration, and significant oliguria. In the same rats, plasma AVP decreased significantly from 5.7 to 3.0 pg/mL. In addition, recovery of apical AQP2 expression was noted in a proportion of epithelial cells of the collecting ducts. Although Li+ in the renal medulla was slightly lower in rats with Li nephropathy treated with furosemide, statistical significance was not achieved. Conclusions. Our results suggest that dehydration or high plasma AVP results in an enhanced rBSC1 expression in Li nephropathy, and that rBSC1 expression is closely associated with the adverse effects of Li ions on collecting duct function.
AB - Background. Renal urinary concentration is associated with enhanced expression of rBSC1, a rat sodium cotransporter, in the thick ascending limb of Henle. Increased expression of rBSC1 was reported recently in nephrogenic diabetes insipidus induced by lithium chloride (Li nephropathy). However, the pathophysiological implication of altered rBSC1 expression has not yet been investigated. Methods. Li nephropathy was induced in rats by an oral administration of 40 mmol lithium/kg dry food. In rats with reduced urinary osmolality to less than 300 mOsm/kg H2O, we examined the expression of rBSC1 mRNA and protein, plasma arginine vasopressin (AVP) and RNA expression of kidney-specific water channel, aquaporin-2 (AQP2), of collecting ducts. Rats with Li nephropathy were treated with furosemide (3 mg/kg body weight), which blocks the activity of rBSC1, and changes in urine concentration, plasma AVP, medullary accumulation of Li ions, and apical AQP2 expression were determined. Results. Rats with Li nephropathy showed increased rBSC1 RNA and protein expression and reduced AQP2 RNA. In these rats, furosemide, which induces dilution of urine and polyuria in normal rats, resulted in a progressive and significant rise in urine osmolality from 167 ± 11 (mean ± SD) at baseline to 450 ± 45 mOsm/kg H2O at three hours after administration, and significant oliguria. In the same rats, plasma AVP decreased significantly from 5.7 to 3.0 pg/mL. In addition, recovery of apical AQP2 expression was noted in a proportion of epithelial cells of the collecting ducts. Although Li+ in the renal medulla was slightly lower in rats with Li nephropathy treated with furosemide, statistical significance was not achieved. Conclusions. Our results suggest that dehydration or high plasma AVP results in an enhanced rBSC1 expression in Li nephropathy, and that rBSC1 expression is closely associated with the adverse effects of Li ions on collecting duct function.
KW - Collecting duct
KW - Furosemide
KW - Sodium transport
KW - Thick ascending limb of Henle
KW - Water channel
KW - cAMP
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U2 - 10.1046/j.1523-1755.2003.00738.x
DO - 10.1046/j.1523-1755.2003.00738.x
M3 - Article
C2 - 12472779
AN - SCOPUS:6444245210
VL - 63
SP - 165
EP - 171
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 1
ER -
