INVOLVEMENT OF K-OXIDE IN THE RAT JEJUNUM IN-VIVO( CHANNEL MODULATIONIN THE PROABSORPTIVE EFFECT OF NITRIC)

The role of K+ channels in the mediation of the nitric oxide(NO)-induc ed proabsorptive effect in intestinal fluid transport was investigated in a functional study, using a model of ligated jejunal loops of anae sthetized rats in vivo. The K+ channel opener cromakalim and the K+ ch annel blocker glibenclamide were administered under basal conditions a s well as under conditions, when fluid secretion was influenced by N-o mega-nitro-L-arginine methyl ester (L-NAME), prostaglandin E(2), Esche richia coli heat stable enterotoxin a (E. coli STa) or L-arginine. int ravenous infusion of cromakalim (63.5 mu g/kg per min) significantly e nhanced net fluid absorption compared to controls, totally abolished n et fluid secretion induced by L-NAME (0.55 mg/kg per min), reversed ne t fluid secretion induced by intraluminal instillation of E. coli STa (10 units/ml) to absorption, but did not influence fluid secretion eli cited by close i.a. infusion of prostaglandin E(2) (79 ng/min). Close i.a. infusion of glibenclamide (0.16 mg/kg per min) reversed net fluid absorption to net secretion, blocked the absorptive effect of L-argin ine (8.88 mg/kg per min) and reduced the proabsorptive effect of croma kalim. The secretory effect of L-NAME was not further enhanced by glib enclamide. These results suggest that modulation of basolateral K+ cha nnels by NO is involved in the mediation of its proabsorptive effect, since opening and closure of K+ channels mimicked, respectively counte racted, the action of NO-donors and inhibitors of NO-synthesis on inte stinal fluid transport. The role of prostaglandins in the proabsorptiv e effect of NO remains to be elucidated. These results furthermore sup port the role of K+ channel openers as potential new antidiarrheal dru gs.