NITRIC-OXIDE AND GALLBLADDER MOTOR FUNCTION

Background: The L-arginine: nitric oxide (NO) pathway has been shown t o be important in the regulation of intestinal motility and NO may be the mediator for nonadrenergic noncholinergic (NANC) neurotransmission . Aim: To determine the role of the L-arginine: NO pathway in gall-bla dder motor function, Methods: Strips of fresh bovine and human gall-bl adders were stimulated with cholecystokinin (CCK), The effects of glyc eryl trinitrate (GTN), sodium nitroprusside and Kreb's solution upon C CK-stimulated muscle contraction were examined, The effect of the NO s ynthase inhibitor, L-N-G-monomethyl-arginine (L-NMMA) upon basal muscl e tone was also examined, Ten human gallbladders were immunohistochemi cally stained for nitric oxide synthase (NOS) and product 9.5 to ident ify neurones. Postprandial gall-bladder emptying was measured on separ ate occasions in six healthy volunteers during systemic intravenous in fusion of normal saline; glyceryl trinitrate; sodium nitroprusside (SN P), hydralazine and L-NMMA, Results: In the in vitro study, GTN and SN P significantly reduced the tension of CCK-stimulated muscle contracti on whilst Kreb's solution had no effect. L-NMMA increased tonic and ph asic muscle contractions, Immunohistochemical staining for NOS was con sistently absent in human gall-bladders, In the in vivo study, both GT N and SNP caused significant impairment of gall-bladder emptying; the ejection fraction was only 50% at the end of the study period involvin g these infusates, this contrasted with ejection fractions in excess o f 80% during infusions with hydralazine, saline and L-NMMA. Conclusion : Pharmacological doses of NO donors impair postprandial gall-bladder emptying in vivo and relax gall-bladder smooth muscle in vitro. Howeve r, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall-bladder mot ility.