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Amlodipine, Nitric Oxide, and Platelet Aggregation

Department of Pharmacology 1 Department of Cardiology 2 Department of Experimental Medicine & Biotechnology Postgraduate Institute of Medical Education and Research Chandigarh, India

For reprint information contact: Vinod K Bhargava, PhD Tel: 91 172 74 7585 Fax: 91 172 74 4401 email: medinst{at}pgi.chd.nic.in Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.

This study examined the effect of a single dose of 0.4 mg•kg^–1 amlodipine on platelet aggregation with and without the nitric oxide synthase inhibitor, Nw-nitro-L-arginine. Blood samples were collected from rhesus monkeys at 0, 1, 2, and 6 hours after administration of amlodipine. Aggregation in platelet-rich plasma was stimulated by 10 µM adenosine diphosphate, 20 µM epinephrine, or 2 µg•mL^–1 collagen. Administration of Nw-nitro-L-arginine alone significantly increased platelet aggregation for up to 2 hours. This effect was antagonized by amlodipine administered 30 minutes after Nw-nitro-L-arginine. The findings suggest that in platelet-rich plasma, the inhibition of platelet aggregation by amlodipine might be mediated by nitric oxide, a potent endogenous inhibitor of aggregation.