Nitric oxide and gall-bladder motor function.
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.


OBJECTIVE
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-NG-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 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.


CONCLUSIONS
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.
Luman
W
W
Gastrointestinal Unit, Western General Hospital, Edinburgh, Scotland, UK.
Ardill
J E
JE
Armstrong
E
E
Smith
G D
GD
Brett
L
L
Lessells
A M
AM
Haynes
W G
WG
Gray
G A
GA
Mickley
E J
EJ
Webb
D J
DJ
Palmer
K R
KR
D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism; D016473:Gallbladder Emptying / Q000187:drug effects / Q000502:physiology*; D005768:Gastrointestinal Hormones / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019518:Postprandial Period; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005768:Gastrointestinal Hormones; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase