High dose vitamin D3 attenuates the hypocalciuric effect of thiazide in hypercalciuric rats.
Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D(28K), and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D(3). Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D.
Jang
Hye Ryoun
HR
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee
Jay Wook
JW
Kim
Sejoong
S
Heo
Nam Ju
NJ
Lee
Jeong Hwan
JH
Kim
Hyo Sang
HS
Jung
Ji Yong
JY
Oh
Yun Kyu
YK
Na
Ki Young
KY
Han
Jin Suk
JS
Joo
Kwon Wook
KW
D000818:Animals; D002118:Calcium / Q000627:therapeutic use / Q000652:urine; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002762:Cholecalciferol / Q000633:toxicity*; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D053565:Hypercalciuria / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
D015220:Calcium Channels; C578716:Slc12a1 protein, rat; C495676:Slc5a1 protein, rat; C000613387:Slc9a3 protein, rat; D049993:Sodium Chloride Symporter Inhibitors; D051269:Sodium-Glucose Transporter 1; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D050916:TRPV Cation Channels; C492241:TRPV5 protein, rat; D006852:Hydrochlorothiazide; D002762:Cholecalciferol; D002118:Calcium
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