Thiazide diuretics normalize urinary calcium in spontaneously hypertensive male rats

Abstract

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 μmol per μmol creatinine, P < 0.01) and sodium (12.6 ± 1.27 vs. 7.89 ± 0.926 μmol per μmol 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.