Abstract | BACKGROUND: METHODS: RESULTS: We noted a markedly high expression of rBSC1 during the development of hyponatremia, and a relatively low expression during vasopressin escape. OPC-31260 administration elevated serum sodium level in a dose-dependent manner. The therapeutic effect, however, declined with increasing number of treatment days, and doses higher than 15 mg/kg/day induced severe toxicity. The physiologic parameters and the alterations of AQP2 and rBSC1 expression during the treatment demonstrated reactions that were completely opposite to those of vasopressin escape. Combination of a furosemide (100 mg/kg/day) and a low dose of OPC-31260 (5 mg/kg/day) additively elevated serum sodium level and sustained the elevated serum sodium level by significantly reducing sodium accumulation in the renal medulla. CONCLUSION: AVP-induced alterations of rBSC1 expression, as well as those of AQP2, are involved in the pathogenesis of SIADH. The pharmacologic blockade of AVP stimulus in SIADH limits its therapeutic efficacy by discontinuing the vasopressin escape, and the selective inhibition of rBSC1 complements this limitation.
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Authors | Itsuro Kazama, Ryo Hatano, Mari Michimata, Katsuya Suzuki, Tomohiro Arata, Michiko Suzuki, Noriyuki Miyama, Akira Sato, Susumu Satomi, Yutaka Ejima, Sei Sasaki, Mitsunobu Matsubara |
Journal | Kidney international
(Kidney Int)
Vol. 67
Issue 5
Pg. 1855-67
(May 2005)
ISSN: 0085-2538 [Print] United States |
PMID | 15840033
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antidiuretic Hormone Receptor Antagonists
- Aqp2 protein, rat
- Aquaporin 2
- Aquaporins
- Benzazepines
- Diuretics
- Receptors, Vasopressin
- Slc12a1 protein, rat
- Sodium Potassium Chloride Symporter Inhibitors
- Sodium-Potassium-Chloride Symporters
- Solute Carrier Family 12, Member 1
- Water
- mozavaptan
- Furosemide
- Urea
- Sodium
- Deamino Arginine Vasopressin
- Potassium
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Topics |
- Animals
- Antidiuretic Hormone Receptor Antagonists
- Aquaporin 2
- Aquaporins
(metabolism)
- Benzazepines
(administration & dosage)
- Deamino Arginine Vasopressin
(administration & dosage)
- Diuretics
(administration & dosage)
- Furosemide
(administration & dosage)
- Hyponatremia
(drug therapy, etiology, metabolism)
- Inappropriate ADH Syndrome
(complications, metabolism)
- Kidney Medulla
(drug effects, metabolism)
- Male
- Potassium
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Receptors, Vasopressin
(metabolism)
- Sodium
(blood, metabolism)
- Sodium Potassium Chloride Symporter Inhibitors
- Sodium-Potassium-Chloride Symporters
(metabolism)
- Solute Carrier Family 12, Member 1
- Urea
(metabolism)
- Water
(administration & dosage)
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