TY - JOUR
T1 - Nitric oxide and gall-bladder motor function
AU - Luman, W.
AU - Ardill, J. E.F.
AU - Armstrong, E.
AU - Smith, G. D.
AU - Brett, L.
AU - Lessells, A. M.
AU - Haynes, W. G.
AU - Gray, G. A.
AU - Mickley, E. J.
AU - Webb, D. J.
AU - Palmer, K. R.
PY - 2001/12/25
Y1 - 2001/12/25
N2 - Background: 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-N(G)- monomethyl-arginine (L-NMMA) upon basal muscle tone was also examined. Ten human gallbladders 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 in vitro 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 in vivo 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 in vivo and relax gall-bladder smooth muscle in vitro. However, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall-bladder motility.
AB - Background: 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-N(G)- monomethyl-arginine (L-NMMA) upon basal muscle tone was also examined. Ten human gallbladders 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 in vitro 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 in vivo 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 in vivo and relax gall-bladder smooth muscle in vitro. However, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall-bladder motility.
UR - http://www.scopus.com/inward/record.url?scp=15644373335&partnerID=8YFLogxK
UR - https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2036.1998.00322.x
U2 - 10.1046/j.1365-2036.1998.00322.x
DO - 10.1046/j.1365-2036.1998.00322.x
M3 - Article
C2 - 9663721
AN - SCOPUS:15644373335
SN - 0269-2813
VL - 12
SP - 425
EP - 432
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 5
ER -