Inhibition of platelet activity in vivo by amlodipine alone and combined with aspirin

Abstract

Platelets are known to contribute to the initiation and progression of coronary artery narrowing by atherosclerotic plaques. Platelets also initiate periodic occlusive coronary arterial thrombosis that leads to unstable angina and myocardial infarction. Aspirin is the most widely used platelet inhibitor. However, if blood levels of epinephrine are elevated, some of the platelet inhibition produced by aspirin is diminished. Amlodipine, a second generation dihydropyridine calcium channel blocker, was studied in a widely used dog model of experimental coronary artery thrombosis. Amlodipine 1 mg/kg alone or amlodipine 0.4 mg/kg with 5 mg/kg of aspirin IV completely abolished the experimental coronary thrombosis and prevented the exacerbation of coronary thrombosis by epinephrine 0.2 μg/kg/min. This protective effect did not appear until 60 minutes after the amlodipine was given, suggesting a delayed onset of action. Long-acting dihydropyridine calcium channel blockers are used in patients with hypertension, angina, and coronary artery disease. They also may offer the patient some protection against fatal or nonfatal myocardial infarction via their platelet-inhibiting effects.