Abstract
Precipitation of myocardial ischemia after withdrawal of calcium channel blocking drugs has been observed in some patients, but the mechanism of this phenomenon is not known. Among 15 patients with coronary artery disease who had been treated with nisoldipine, onset of severe unstable angina was observed in 2 and evolution of acute myocardial infarction in 1 patient after abrupt withdrawal of nisoldipine therapy. To determine a mechanism of myocardial ischemia after cessation of nisoldipine therapy, the status of α 2 adrenoceptors and platelet sensitivity to epinephrine was examined in 5 patients. After 6 weeks of therapy, there were no changes in the number of α 2 adrenoceptors (199 ± 45 vs 188 ± 35 fmol/mg protein, mean ± standard error of the mean) or affinity for antagonist (dissociation constant 5.78 ± 0.99 vs 4.70 ± 0.87 n M), but there was a significant (p < 0.01) increase in the affinity of α 2 adrenoceptors for agonist epinephrine. In vitro platelet sensitivity to epinephrine, but not ADP, also increased markedly. It is postulated that an increase in α 2-adrenoceptor affinity for agonist may relate to platelet hyperactivity, which may result in severe myocardial ischemia upon withdrawal of calcium blocking drugs in some patients.
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