Aldosterone Reduces Crypt Colon Permeability during Low-Sodium Adaptation

Abstract

Fluid and electrolyte absorption by colonic crypts depends on the transport properties of crypt cellular and paracellular routes and of the pericryptal sheath. As a low-Na(+) diet increases aldosterone and angiotensin II secretion, either hormone could affect absorption. Control and adrenalectomized (ADX) Sprague-Dawley rats were kept at a high-NaCl (HS) diet and then switched to low-NaCl (LS) diet for 3 days. Aldosterone or angiotensin II plasma concentrations were maintained using implanted osmotic mini-pumps. The extracellular Na(+) concentration in isolated rat distal colonic mucosa was determined by confocal microscopy using a low-affinity Na(+) -sensitive fluorescent dye (Sodium red, and Na(+) -insensitive BODIPY) bound to polystyrene beads. Crypt permeability to FITC-labelled dextran (10 kDa) was monitored by its rate of escape from the crypt lumen into the pericryptal space. Mucosal ion permeability was estimated by transepithelial electrical resistance (TER) and amiloride-sensitive short-circuit current (SCC). The epithelial Na(+) channel, ENaC, was determined by immunolocalization. LS diet decreased crypt wall permeability to dextran by 10-fold and doubled TER. Following ADX, aldosterone decreased crypt wall dextran permeability, increased TER, increased Na(+) accumulation in the pericryptal sheath and ENaC expression even in HS. Infusion of angiotensin II to ADX rats did not reverse the effects of aldosterone deprivation. These findings indicate that aldosterone alone is responsible for both the increase in Na(+) absorption and the decreased paracellular and pericryptal sheath permeability.

Aldosterone induces myofibroblast EGF secretion to regulate epithelial colonic permeability

“…Experimental procedures were approved by the Ethical Committee for Animal Experimentation of the University of Barcelona and the Catalan government and comply with the European Union regulation on animal experimentation. The protocol was similar to that described previously (17). All animals received a high-Na diet (wheat and barley and 150 mM NaCl in drinking water) for 4 days.…”

“…These effects are partly due to the upregulation of the epithelial sodium channel (ENaC) and changes in the barrier function of the pericryptal sheath, as has been shown in both rat and mouse descending colonic crypts (18,32). Within 3 days of transition from high-Na to low-Na, the rat colonic crypt wall becomes less permeable to dextran and the pericryptal space can accumulate a much higher Na concentration (17). Vasopressin also has trophic effects on the rat distal colon, increasing pericryptal myofibroblast growth, and these effects are independent of Aldo (5).…”

“…Low-Na adaptation increased the expression of ␣-smooth muscle actin, specific adhesion molecules such as OB-cadherin, and collagen IV in the pericryptal sheath (4, 17, 33), and also resulted in functional changes in the crypt epithelium, including increased expression of junctional proteins such as claudin IV and E-cadherin. These effects were mediated by the mineralocorticoid receptor (MR) because spironolactone (SPI) prevented the effects of Aldo (4,17).This study focuses on the mechanisms of the effects of Aldo on colonic absorptive function during low-Na adaptation. We wanted to ascertain whether the effects on pericryptal sheath growth and epithelial permeability observed in vivo were directly attributable to Aldo or indirectly through mediators delivered by either the epithelial mucosa or myofibroblasts in response to Aldo regulation.…”

“…Low-Na adaptation increased the expression of ␣-smooth muscle actin, specific adhesion molecules such as OB-cadherin, and collagen IV in the pericryptal sheath (4, 17, 33), and also resulted in functional changes in the crypt epithelium, including increased expression of junctional proteins such as claudin IV and E-cadherin. These effects were mediated by the mineralocorticoid receptor (MR) because spironolactone (SPI) prevented the effects of Aldo (4,17).…”

“…Experiments conducted on adrenalectomized rats on low-Na and high-Na diets, implanted with osmotic pumps perfusing either Aldo or ANG II, showed that Aldo acts as a trophic agent on the myofibroblast layer and that ANG II has no direct role in this process (4,17). Low-Na adaptation increased the expression of ␣-smooth muscle actin, specific adhesion molecules such as OB-cadherin, and collagen IV in the pericryptal sheath (4,17,33), and also resulted in functional changes in the crypt epithelium, including increased expression of junctional proteins such as claudin IV and E-cadherin.…”