Smith, Graeme DrummondGraeme DrummondSmithLuman, W.Ardill, J. E. F.Armstrong, E.Brett, L.Lessells, A. M.Haynes, W. G.Gray, G. A.Mickley, E. J.Webb, D. J.Palmer, K. R.2021-11-182021-11-181998https://repository.sfu.edu.hk/handle/sfu/1810Background The L-arginine: nitric oxide (NO) pathway has been shown to 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-bladder motor function. Methods Strips of fresh bovine and human gall-bladders were stimulated with cholecystokinin (CCK). The effects of glyceryl trinitrate (GTN), sodium nitroprusside and Kreb's solution upon CCK-stimulated muscle contraction were examined. The effect of the NO synthase inhibitor, L-<i>N</i>^G-monomethyl-arginine (L-NMMA) upon basal muscle tone was also examined. Ten human gall-bladders were immunohistochemically stained for nitric oxide synthase (NOS) and product 9.5 to identify neurones. Postprandial gall-bladder emptying was measured on separate occasions in six healthy volunteers during systemic intravenous infusion of normal saline; glyceryl trinitrate; sodium nitroprusside (SNP), hydralazine and L-NMMA. Results In the <i>in vitro</i> study, GTN and SNP significantly reduced the tension of CCK-stimulated muscle contraction whilst Kreb's solution had no effect. L-NMMA increased tonic and phasic muscle contractions. Immunohistochemical staining for NOS was consistently absent in human gall-bladders. In the <i>in vivo</i> study, both GTN and SNP caused significant impairment of gall-bladder emptying; the ejection fraction was only 50% at the end of the study period involving these infusates, this contrasted with ejection fractions in excess of 80% during infusions with hydralazine, saline and L-NMMA. Conclusion Pharmacological doses of NO donors impair postprandial gall-bladder emptying <i>in vivo</i> and relax gall-bladder smooth muscle <i>in vitro</i>. However, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall-bladder motility.enjournal article10.1046/j.1365-2036.1998.00322.x