Effect of nitric oxide/cyclic guanosine mono-phosphate pathway on gallbladder relaxant response in bile duct-ligated guinea pigs.
OBJECTIVE
Common bile duct ligation (CBDL) in the guinea pig is a well-defined model of acalculous cholecystitis. Nitric oxide (NO) mediates smooth muscle relaxation by stimulating the activity of soluble guanylate cyclase. The aim of this study was to determine whether the NO/cyclic guanosine monophosphate pathway plays a role in gallbladder relaxant response after CBDL.


METHODS
Relaxant response of gallbladder muscle strips from CBDL and sham-operated guinea pigs was studied in vitro. Animals were treated with saline, aminoguanidine or an aminoguanidine + L-arginine combination in vivo. Concentration-response curves of papaverine, diethylamine/NO, YC-1, sildenafil and amrinone were obtained and relaxations in each group were calculated as the percent of the contractions induced by carbachol (10(-6) M).


RESULTS
There was a significant decrease in the gallbladder muscle relaxant responses to these substances in CBDL and aminoguanidine groups compared with sham surgical controls. The decreased relaxant response was reversed by aminoguanidine + L-arginine but not by aminoguanidine alone.


CONCLUSIONS
Decreased relaxant responses might be due to the reduced guanylate cyclase enzyme activity, but further studies are required.
Aydin
C
C
Department of General Surgery, Cumhuriyet University School of Medicine, Sivas, Turkey. caydin@cumhuriyet.edu.tr
Bagcivan
I
I
Yildirim
S
S
Koyuncu
A
A
Topcu
O
O
Soylu
S
S
Ozer
H
H
D000676:Amrinone / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001652:Bile Ducts / Q000502:physiology / Q000601:surgery; D006152:Cyclic GMP / Q000502:physiology*; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology*; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D008026:Ligation; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology
D006146:Guanidines; D006834:Hydrazines; D007191:Indazoles; D020030:Nitric Oxide Donors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D001120:Arginine; D000068677:Sildenafil Citrate; D010208:Papaverine; D006152:Cyclic GMP; D000676:Amrinone; C004479:pimagedine