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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.

japanese journal of pharmacology/japanese journal of pharmacology

Perfusion-time-dependent appearance of blocking effect of diltiazem on norepinephrine-induced vasoconstriction in isolated, perfused dog pulmonary veins.