Antagonism of Ca2+-Induced Constriction of Isolated Rabbit Ear Artery by Nitrendipine in High K+- and/or Norepinephrine-Containing Medium

Nitrendipine is a Ca2+ channel antagonist with vasodilator and antihypertensive properties. In the present experiments, the isolated rabbit ear artery was perfused with Ca2+-free Krebs-bicarbonate solution. Constriction of the artery was induced by addition of Ca2+ to perfusion fluid in the presence of KCl (75 mM, high K+), norepinephrine (NE) at various concentrations, or high K+ and NE. Nitrendipine produced concentration-dependent inhibition of the constrictor response to Ca2+ in high K+ medium. NE, added to high K+ medium, reversed the inhibitory effect of nitrendipine. In NE-containing medium, nitrendipine also inhibited the constrictor effect of Ca2+. Nitrendipine-induced inhibition was inversely proportional to the concentration of NE in the medium. The inhibitory effect of nitrendipine in the medium containing high K+ and NE was significantly less pronounced than in normal K+- and NE-containing medium. The experiments demonstrate relative resistance of "receptor-operated" channels to nitrendipine and suggest that under depolarizing conditions these channels may operate more effectively.