Perfusion-Time-Dependent Appearance of Blocking Effect of Diltiazem on Norepinephrine-lnduced Vasoconstriction in Isolated, Perfused Dog Pulmonary Veins

Time-dependent changes in the blocking effect of diltiazem on norepinephrine (NE)-induced vasoconstrictions were investigated in isolated canine pulmonary veins. Within 2-3 hr of the perfusion period, pretreatment with diltiazem did not affect the vasoconstrictor responses to NE. However, in the 8-11 hr perfused preparations, diltiazem suppressed the NE-induced vasoconstriction significantly. It may participate in the mechanisms for the appearance of the blocking effect in the following manner: 1 ) a proportion of alpha adrenoceptors which are sensitive to calcium entry are increased and/or 2) spare alpha adrenoceptors are decreased time-dependently.