The functional changes in rat colon on transition from high sodium (HS) diet (about 3600 µmol NaCl/day) to low sodium (LS) diet (about 35 µmol NaCl/day) involve decreased crypt wall permeability to 10 kDa dextran and increased Na⁺ accumulation from 144 ± 4 mM (HS; mean ± S.E.M., n = 4) to 285 ± 7 mM (LS after 3 days; n = 4) in the pericryptal sheath. There are also trophic changes in the pericryptal myofibroblastic sheath within 3 days of transition from HS to LS diet (Naftalin et al. 2003). We now observe the effects of the angiotensin converting enzyme inhibitor captopril, the angiotensin II receptor type I inhibitor losartan and the aldosterone antagonist spironolactone.

The effects of the following treatments were studied on Sprague-Dawley rats (190-220 g) fed HS diet for 8-9 days then switched to LS diet for 3 or 5 days: (a) captopril at 80 mg kg-1 day-1; (b) losartan at 30 mg kg-1 day-1 and (c) spironolactone at 30 mg kg-1 day^-1. Drug administration commenced 2 days before switching to the LS diet. [Na⁺] in isolated rat distal colonic mucosa was determined by confocal microscopy using a low affinity Na⁺-sensitive dye (Sodium Red, and BODIPY) bound to polystyrene beads (Jayaraman et al. 2001). Crypt permeability to dextran was monitored by the rate of escape of FITC labelled dextran (10 kDa) from the crypt lumen into the pericryptal space at 37°C. Experiments were approved by the Ethical Committee of the University of Barcelona.

Adaptation to the LS diet reduced urinary volume from 8.6 ± 0.8 ml day^-1 (HS condition; mean ± S.E.M., n = 3) to 5.1 ± 1 ml day^-1 (n = 5). After 5 days in the LS diet, water excretion was significantly increased by captopril (10.1 ± 1 ml day^-1; n = 3), losartan (46 ± 8 ml day^-1; n = 3) and spironolactone (44 ± 11 ml day^-1; n = 3). Na⁺ excretion in rats fed the HS diet (2394 ± 187 µmol day^-1; n = 3) was reduced to 12 ± 1.5 µmol day^-1 (n = 3) in the LS condition. Drugs induced significant increases in urinary Na⁺ excretion to 25.9 ± 4.2 µmol day^-1 (captopril; n = 3), 35.6 ± 2.1 µmol day^-1 (losartan; n = 3) and 26.8 ± 1 µmol day^-1 (spironolactone; n = 3). Urinary excretion rate of aldosterone (AER) was raised from 50 pmol day^-1 in HS adapted animals to 180 pmol day^-1 in the LS fed rats. Captopril decreased AER to 55 pmol day^-1, losartan had no effect (171 pmol day^-1) and spironolactone caused a large increase in AER (288 pmol day^-1). All three treatments prevented the increase in myofibroblast growth, already seen after 3 days in LS diet, as shown by the 70-80% decrease in smooth muscle actin content of the pericryptal sheath myofibroblast smooth muscle actin content in drug-treated animals compared with untreated rats. The Increase in pericryptal [Na⁺] and decrease in crypt dextran permeability seen 3 days after adaptation to LS diet were also reduced by all drug treatments. The similar nullifying effects of the drugs assayed on adaptation from HS to LS indicate that aldosterone and angiotensin II have linked effects at least on the trophic response of the colon to the LS diet.

This work was supported by The Wellcome Trust.