Thiazide diuretics normalize urinary calcium in spontaneously hypertensive male rats.
The role of the thiazide-sensitive distal convoluted tubule (DCT) in the hypercalciuria of the spontaneously hypertensive rat (SHR) strain was examined by determining (a) the renal density of the thiazide diuretic receptor with 3H-metolazone, and (b) the renal response to a maximal dose of bendroflumethiazide (BFTZ). We confirm that the renal thiazide receptor density was greater in SHR than WKY (0.936 +/- 0.026 vs. 0.797 +/- 0.045 pmol/mg protein; P = 0.02). Prior to BFTZ the urinary excretion of calcium (0.525 +/- 0.061 vs. 0.274 +/- 0.049 micromol per micromol creatinine, P < 0.01) and sodium (12.6 +/- 1.27 vs. 7.89 +/- 0.926 micromol per micromol creatinine; P < 0.01) were greater in SHR versus WKY. BFTZ decreased the excretion of calcium only in SHR and to a level (0.250 +/- 0.032) not significantly different (P = 0.519) from WKY (0.225 +/- 0.032). Surprisingly, BFTZ increased chloride excretion to a greater extent in WKY than in SHR (P = 0.008). We postulate that hypercalciuria in SHR is a manifestation of incomplete uptake of calcium from the tubule lumen across the apical cell membrane in the DCT of the SHR nephron.
Fanestil
D D
DD
Department of Medicine, School of Medicine, University of California San Diego, La Jolla, USA.
Vaughn
D A
DA
Ma
L
L
Hyde
R H
RH
Printz
M P
MP
D000818:Animals; D001539:Bendroflumethiazide / Q000494:pharmacology*; D002118:Calcium / Q000652:urine*; D002712:Chlorides / Q000652:urine; D004232:Diuretics; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000652:urine*; D017136:Ion Transport / Q000187:drug effects; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*
D002712:Chlorides; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D001539:Bendroflumethiazide; D002118:Calcium