Laboratory Investigation

Kidney International (1990) 37, 1248–1255; doi:10.1038/ki.1990.108

Effect of furosemide on water and urea transport in cortical and inner medullary collecting duct

Lúcia H Kudo1, Alfred A van Baak1 and Antonino S Rocha1

1Laboratório de Pesquisa Básica do Departamento de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo, Brazil

Correspondence: Antonino S Rocha MD, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, CEP 01246, São Paulo, Brazil.

Received 18 November 1988; Revised 11 December 1989; Accepted 18 December 1989.

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Abstract

Effect of furosemide on water and urea transport in cortical and inner medullary collecting duct. The present in vitro microperfusion study examined whether furosemide has an effect on hydraulic conductivity (Lp times 10-6cm/sec dot atm) and 14C-urea permeability (Pu times 10-5cm/sec) in inner medullary collecting ducts (IMCD) and cortical collecting tubules (CCT) isolated from rat and rabbit kidneys. Furosemide added to the bath fluid decreased arginine-vasopressin (AVP)-stimulated Lp of rat IMCD in a dose-dependent manner, with the threshold effect at 10-6 M. Furosemide (10-4 M) reduced Lp from 20.5 plusminus 2.3 to 12.1 plusminus 1.2 (P < 0.01) reversibility, but had no effect when added to the perfusate. In addition, furosemide reduced dibutyryl cyclic AMP-stimulated Lp from 20.3 plusminus 1.1 to 11.2 plusminus 1.6 (P < 0.01). This effect of furosemide was also observed with indomethacin, a PGE2 synthesis inhibitor. The addition of indomethacin (10-4 M) to AVP (50 muU/ml) increased Lp from 24.7 plusminus 2.3 to 29.7 plusminus 2.8 (P < 0.001), which was reduced to 20.3 plusminus 2.6 (P < 0.001) when furosemide was added to indomethacin in the bath. The inhibitory effect of furosemide on AVP-stimulated Lp was also observed in rabbit IMCD (Lp decreased from 12.8 plusminus 0.8 to 5.15 plusminus 1.46, P < 0.02), but it was not observed in the CCT isolated from rabbit kidneys (7.96 plusminus 1.87 with AVP vs. 7.94 plusminus 1.41 with AVP + furosemide). Furthermore, in rat IMCD the stimulatory effect of AVP on Pu from 7.7 plusminus 0.4 to 26.8 plusminus 1.3 was reduced by furosemide to 19.7 plusminus 1.2 (P < 0.01). Thus, furosemide in the peritubular fluid was able to decrease the stimulatory action of AVP on H2O and urea permeabilities in rat and rabbit IMCD, but not in rabbit CCT. This effect of furosemide appears to be independent of PGE2 and it occurs at a step distal to cyclic AMP formation.

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