Iron deficiency diminishes gallbladder neuronal nitric oxide synthase

Background, Iron deficiency has been demonstrated in the prairie dog to res ult in cholesterol crystal formation and altered biliary motility. Gallblad der filling and emptying are influenced by both inhibitory and excitatory s timuli, with nitric oxide (NO) playing a key role in normal relaxation, Iro n is a cofactor for nitric oxide synthase. Therefore, we tested the hypothe sis that iron deficiency would result in diminished levels of gallbladder n euronal nitric oxide synthase (nNOS) but would not influence the gallbladde r's response to excitatory stimuli. Materials and methods. Twenty adult female prairie dogs were fed either an iron-supplemented (Fe+) (200 ppm) control diet (n = 10) or an iron-deficien t (Fe-) (8 ppm) diet (n = 10) for 8 weeks. Fasting gallbladder volume was m easured. Gallbladder muscle strips were harvested for response to excitator y stimuli and measurement of nNOS protein levels by Western blotting. Muscl e strip response to a spectrum of doses of cholecystokinin, acetylcholine, and electrical held stimuli was determined, and the areas under the respons e curves were calculated. Results. Gallbladder volume increased in the iron-deficient prairie dogs co mpared with the iron-supplemented group (1.45 +/- 0.27 mL vs 0.80 +/- 0.13 mL, P < 0.05). Iron deficiency diminished the ratio of gallbladder nNOS to beta-actin protein levels (0.05 +/- 0.01 vs 3.48 +/- 1.02, P < 0.05) but re sulted in a normal response to excitatory stimuli. Conclusions. We conclude that diminished gallbladder neuronal nitric oxide synthase contributes to the gallbladder stasis that occurs with iron defici ency. This phenomenon may contribute to the increased incidence of gallston es in premenopausal women. (C) 2000 Academic Press.