Adrenal steroids stimulate thiazide-sensitive NaCl transport by rat renal distal tubules.
The current experiments were designed to test the hypothesis that adrenal steroids increase thiazide-sensitive Na and Cl transport by the mammalian renal distal convoluted tubule (DCT). Male Sprague-Dawley rats were adrenalectomized and received steroid hormones by osmotic pumps. Six groups of animals were studied as follows: group I, no hormones; group II, replacement levels of dexamethasone only; group III, replacement levels of aldosterone only; group IV, replacement levels of both hormones; group V; replacement levels of aldosterone and high levels of dexamethasone; and group VI, replacement levels of dexamethasone and high levels of aldosterone. Circulating levels of both hormones were found to be in the high physiological range when infused at the high rate. In vivo microperfusion of distal tubules was performed to determine rates of Na and Cl transport. Chlorothiazide was used to assess the magnitude of electroneutral Na-Cl cotransport. Both aldosterone and dexamethasone stimulated thiazide-sensitive Na and Cl transport by the distal tubule by more than fivefold. [3H]metolazone binding was measured to assess the number of thiazide-sensitive Na-Cl cotransporters in renal cortex. Each steroid also increased the number of [3H]metolazone binding sites in kidney cortex more than threefold. The results are consistent with the presence of both mineralocorticoid and glucocorticoid receptors in the mammalian DCT. Physiological changes in circulating levels of adrenal steroids may affect renal NaCl excretion in part by regulating the rate of electroneutral Na-Cl absorption by the DCT.
Velázquez
H
H
Yale University School of Medicine, New Haven 06510, USA.
Bartiss
A
A
Bernstein
P
P
Ellison
D H
DH
D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002740:Chlorothiazide / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004338:Drug Combinations; D007672:Kidney Cortex / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D008297:Male; D008788:Metolazone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D049992:Sodium Chloride Symporters; D027981:Symporters
D002352:Carrier Proteins; D004338:Drug Combinations; D049992:Sodium Chloride Symporters; D027981:Symporters; D000450:Aldosterone; D002740:Chlorothiazide; D003907:Dexamethasone; D008788:Metolazone