Relative effects of dihydropyridine L-type calcium channel antagonism on biliary, duodenal, and vascular tissues: an in vivo and in vitro analysis in Australian brush-tailed possum.
Nifedipine is used to treat sphincter of Oddi dysfunction. Its effects on the biliary system and duodenum in relation to its known vascular actions are unclear. Our aims were to determine the relative tissue sensitivities to dihydropyridine L-type calcium channel antagonism in the sphincter of Oddi, gallbladder, duodenum, and vasculature. For in vivo studies, 23 possums received nifedipine at three different doses with blood pressure and sphincter of Oddi manometry recordings. For in vitro studies, tissues from 28 possums were pretreated with nicardipine (10(-8)-10(-5) M) and cumulative concentrations of agonist were administered (carbachol, norepinephrine at 10(-9)-10(-5) M). In in vivo studies, blood pressure fell significantly at a lower dose than sphincter of Oddi motility. In in vitro studies, the sphincter of Oddi was more sensitive than arterial tissue, with the duodenum especially sensitive. In conclusion, in the possum we found that L-type channel antagonism in vivo was more potent to the vasculature than the sphincter of Oddi but this was not confirmed in vitro.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D004386:Duodenum / Q000187:drug effects*; D005260:Female; D005704:Gallbladder / Q000187:drug effects*; D008297:Male; D008365:Manometry; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D009893:Opossums; D009803:Sphincter of Oddi / Q000187:drug effects*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009529:Nicardipine; D009543:Nifedipine