Nifedipine inhibits cholecystokinin-induced gallbladder contraction.
Nifedipine is a calcium channel blocker which results in relaxation of smooth muscle. Although it has been utilized clinically to treat cardiovascular disease, and more recently spastic disorders of the esophagus and colon, its effects on gallbladder contractility have not been clearly defined. We tested the effects of nifedipine on gallbladder contraction stimulated by cholecystokinin (CCK) in a conscious guinea pig model and in healthy human volunteers. Gallbladder contraction was measured in response to repeated injections of CCK before and after intravenous nifedipine given to groups of five guinea pigs in a dose of 100, 200, or 300 micrograms. Nifedipine virtually abolished spontaneous interdigestive gallbladder contractile activity and decreased resting gallbladder tone. The mean amplitude of gallbladder contraction in response to CCK was decreased by 45, 73, and 67% (P less than 0.01), in response to the nifedipine doses of 100, 200, and 300 micrograms, respectively. The integrated gallbladder contractile response and the rate of rise of gallbladder pressure in response to CCK were also significantly decreased by nifedipine. In nine healthy human volunteers, gallbladder emptying was measured by radionuclide cholescintigraphy in response to CCK infusion; on another day the study was repeated after oral administration of 10 mg nifedipine. Ejection fraction was significantly decreased by nifedipine from 72 +/- 5 to 51 +/- 5% (P less than 0.001). These data demonstrate that nifedipine is a potent inhibitor of gallbladder contractility in guinea pigs and man. This may provide the basis for the use of nifedipine clinically in the treatment of biliary colic and also raises questions about the potential effect of long-term nifedipine use on gallstone formation and cholecystitis.
Clas
D
D
Department of Surgery, McGill University, Montreal, Quebec, Canada.
Hould
F S
FS
Rosenthall
L
L
Arzoumanian
A
A
Fried
G M
GM
D000328:Adult; D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors
D002766:Cholecystokinin; D009543:Nifedipine