Hypercalciuria of mineralocorticoid escape: clearance and micropuncture studies in the rat.
Chronic mineralocorticoid excess results in the predicted retention of salt and water followed by a period of escape from sodium retention and hypercalciuria. We studied a rat model during mineralocorticoid escape (ME) with clearance and micropuncture studies to ascertain the nephron site and possible role of parathyroid hormone. Rats during ME were hypercalciuric compared with a matched saline group. Clearance studies revealed a marked difference in the calcium-to-sodium fractional excretion ratio (FECa/FENa) between saline-expanded and mineralocorticoid (desoxycorticosterone acetate, DOCA)-escaped animals (saline-expanded, 0.40 +/- 0.09 vs. DOCA, 1.02 +/- 0.14; P less than 0.01). The addition of either hydrochlorothiazide (HCTZ) or amiloride (AMIL) to the ME animals significantly lowered this ratio from that seen in the intact ME group (DOCA-HCTZ, 0.47 +/- 0.07; DOCA-AMIL, 0.83 +/- 0.14). Neither parathyroidectomy (PTX) nor parathyroid hormone infusions (PTH) in ME animals altered the FECa/FENa from that seen in the intact ME group (DOCA-PTX, 1.15 +/- 0.20; DOCA-PTH, 1.25 +/- 0.18). Segmental micropuncture along the length of superficial nephrons demonstrated no differences in calcium delivery to late proximal, early distal, and late distal sites. However, FECa was markedly increased in ME animals compared with saline controls (saline, 0.48 +/- 0.13% vs. DOCA, 1.62 +/- 0.24%; P less than 0.05). We conclude that the hypercalciuria of ME is independent of PTH and can be significantly reduced by HCTZ or AMIL. Micropuncture and clearance data suggest that the hypercalciuria of ME is mediated in the terminal nephron. The differences in the results when superimposing various factors that influence distal nephron calcium reabsorption on ME may be related to differences in their site(s) of activity on calcium transport.
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001826:Body Fluids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000652:urine*; D003900:Desoxycorticosterone / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D008901:Mineralocorticoids / Q000378:metabolism* / Q000494:pharmacology; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism / Q000652:urine
D008901:Mineralocorticoids; D010281:Parathyroid Hormone; D006852:Hydrochlorothiazide; D003900:Desoxycorticosterone; D000584:Amiloride; D012964:Sodium; D011188:Potassium; D002118:Calcium