Localization of diuretic action in microperfused rat distal tubules: Ca and Na transport

Abstract

Experiments were performed in rats to examine the distal site of action of thiazide diuretics and the additive hypocalciuric properties of thiazides and amiloride. In clearance experiments, the maximal natriuretic and hypocalciuric dose of chlorothiazide was established. When amiloride was added, there was further augmentation of Ca reabsorption (P less than 0.025) but no additional natriuresis. Amiloride blunted thiazide-induced kaliuresis (P less than 0.001). Localization of the thiazide effect was studied in early and late distal tubules microperfused in vivo with control and thiazide-containing solutions. The maximally effective luminal drug concentration, 5 X 10(-4) M, inhibited Na transport (P less than 0.001) and enhanced Ca transport (P less than 0.01) in the early distal segments; late segments were on the average unaffected. It is suggested that thiazides interact with the distal convoluted tubule cell, whose predominant location is the early distal tubule. In two long distal tubules, with early and late segments, a maximal concentration of chlorothiazide increased Ca transport and decreased Na transport. Addition of 10(-5) M amiloride caused an additional increment in Ca reabsorption. As amiloride's action is located in the late distal tubule, it is suggested from these experiments that a basis for additive hypocalciuric actions of thiazides and amiloride is separate sites of action in the distal tubule.

The sodium chloride cotransporter SLC12A3: new roles in sodium, potassium, and blood pressure regulation

“…In addition, potassium may also be secreted apically by the renal outer medullary potassium channel (ROMK) and a potassium chloride cotransporter [133]. In addition, NCC modulates transcellular magnesium and calcium reabsorption in the DCT through interaction with the transporters TRPM6 and 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 4 TRVP5, respectively (Figure 1) [16,85]. Only 5 to 10% of the filtered load of sodium is reabsorbed in the DCT and this is primarily mediated by NCC [23].…”

Mechanism of calcium transport stimulated by chlorothiazide in mouse distal convoluted tubule cells.

“…The unique ability of these agents to reduce renal calcium excretion, especially upon chronic administration, while simultaneously promoting that of sodium is a long-standing observation (1). Renal clearance (2), micropuncture (3)(4)(5)(6), and microperfusion (7,8) experiments identified the distal convoluted tubule as the nephron site at which thiazide diuretics inhibit sodium transport. Distal convoluted tubules are also the site at which thiazide diuretics stimulate calcium absorption (6).…”

Effect of S-8666 on Cl- Transport in the Rabbit Connecting Tubule Perfused in Vitro.

“…Thiazide diuretics are known to have hypocalciuric action, probably resulting from their action on the distal nephron (Costanzo 1985). Shimizu et al (1991) reported that trichlormethiazide increases Ca2+ flux in the presence of PTH.…”