This paper is only available as a PDF. To read, Please Download here.
Abstract
The present study evaluated the effects of the calcium-channel blocking agent diltiazem
on platelet aggregation and on synthesis of thromboxane B2 (the stable metabolite of thromboxane A2) from platelet-rich plasma (PRP) and whole blood samples. Our results showed that
diltiazem inhibits collagen- and thrombin-induced platelet aggregation and TXB2 production from PRP. Since no significant interference with conversion of arachidonate
to thromboxane A2 was demonstrated, inhibition of phospholipase A2 activity may be the prevailing mechanism of the diltiazem effect. The drug demonstrated
a dose-related inhibitory activity on TXB2 synthesis from whole blood samples during spontaneous clotting or following stimulation
with collagen or thrombin. The present results give further evidences for an antiplatelet
activity of diltiazem and support the hypothesis that inhibition of platelet function
contributes to the therapeutic efficacy of this drug in the treatment of cardiovascular
diseases.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Prostaglandins, Leukotrienes and Essential Fatty AcidsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Thromboxanes a new group of biologically active compounds derived from prostaglandin endoperoxides.in: 2nd ed. Proceedings of the National Academy of Sciences USA. 72. 1975: 2294-2298
- On the formation and effects of thromboxane A2 in human platelets.Acta Physiologica Scandinavica. 1976; 98: 285-294
- Release of prostaglandins and thromboxane into the coronary circulation in patients with ischaemic heart disease.New England Journal of Medicine. 1981; 304: 685-691
- Urinary excretion of 2–3-dinor-thromboxane B2 in and under normal conditions, following drugs and during some pathological conditions.Prostaglandins. 1984; 27: 627-635
- Platelet in unstable coronary disease.New England Journal of Medicine. 1986; 315: 983-989
- Biosynthesis of thromboxane in patients with systemic sclerosis and Raynaud's phenomenon.British Medical Journal. 1986; 292: 1037-1039
- Effect of calcium antagonist diltiazem in patients with variant angina.American Heart Journal. 1981; 101: 719-724
- Inhibition of platelet aggregation by diltiazem: comparison with verapamil and nifedipina and inhibitory potencies of diltiazem metabolites.Circulation Research. 1983; 5: 115-119
- Calcium blocker diltiazem inhibits platelet activation and stimulates vascular prostacyclin synthesis.American Journal Medical Sciences. 1986; 291: 20-24
- Studies on inhibition of human platelet response by diltiazem.General Pharmacology. 1990; 21: 949-954
- Effects of oral diltiazem on platelet function: alone and in combination with low dose aspirin.Thrombosis Research. 1986; 44: 391-400
- Pharmacology of platelet-affecting drugs.Circulation. 1980; 62: V26-V41
- Platelet aggregation.in: Longenecker GL The platelets. Physiology and Pharmacology. Academic Press, Orlando1985: 1
- Polymorphonuclear leukocytes produce thromboxane A2-like activity during phagocytosis.Prostaglandins. 1976; 11: 749-757
- Thromboxane generation by human peripheral blood polymorphonuclear leukocytes.Journal of Experimental Medicine. 1978; 148: 787-792
- Human mononuclear phagocytes from different anatomical sites differ in their capacity to metabolize arachidonic acid.Clinical and Experimental Immunology. 1984; 57: 385-392
- The in vitro effect of amrinone on thromboxane B2 synthesis in human whole blood.Thrombosis Research. 1986; 42: 817-821
- Aggregation of whole blood platelets by adenosine diphosphate and its reversal.Nature. 1962; 194: 927-929
- Methods in dose response platelet aggregometry.Thrombosis and Haemostasis. 1985; 54: 216-218
- Epidemiological characteristics of platelet aggregability.British Medical Journal. 1985; 290: 428-432
- Pharmacokinetics and bioavailability of diltiazem (CRD-401) in dog.Arzneimittel-Forschung/Drug Research. 1977; 27: 1424-1428
- The activation by Ca2+ of platelet phospholipase A2. Effects of dibutyryl cyclic adenosine monophosphate and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate.Biochimica et Biophysica Acta. 1978; 543: 409-422
- Thromboxane formation during blood clotting is decreased by verapamil.Prostaglandins, Leukotrienes and Medicine. 1984; 13: 217-218
- Influence of propranolol on platelet aggregation and thromboxane B2 production from platelet-rich plasma and whole blood.Prostaglandins, Leukotrienes and Essential Fatty Acids. 1989; 36: 1-7
- Comparison of inhibitory action of prostacyclin and a new prostacyclin analogue on the aggregation of human platelets in whole blood.Haemostasis. 1987; 17: 147-151
- Effects of calcium channel blockers on in vitro platelet function in whole blood using single platelet counting.Thrombosis and Haemostasis. 1989; 61: 137-139
- Formation and regulation of platelet and haemostatic plug.Human Pathology. 1987; 18: 111-120
- Platelet clumping produced by connective tissue suspension and by collagen.in: 2nd ed. Proceedings of the Society for Experimental Biology and Medicine. 109. 1963: 779-781
- Mechanisms of bronchoconstriction and of thrombocytopenia induced by collagen in the guinea pig.European Journal of Pharmacology. 1978; 58: 273-284
- A dominant role of thromboxane formation in secondary aggregation of platelets.Nature. 1979; 282: 331-333
- Thromboxane A2 and prostaglandin H2: potent stimulators of the swine coronary artery.Prostaglandins. 1976; 12: 943-950
- Thromboxane release in coronary artery disease: spontaneous versus pacing-induced angina.American Heart Journal. 1984; 107: 286-292
- Thromboxane A2 in vasotonic angina pectoris: evidence from direct measurements and inhibitor trials.New England Journal of Medicine. 1981; 304: 998-1003
- Thrombosis and acute coronary-artery lesions in sudden cardiac ischaemic death.New England Journal of Medicine. 1984; 310: 1137-1140
- Evidence that thromboxane contributes to ventricular fibrillation induced by reperfusion of the ischaemic myocardium.Journal of Molecular and Cellular Cardiology. 1982; 14: 483-488
Article info
Publication history
Accepted:
April 25,
1991
Received:
January 3,
1991
Identification
Copyright
© 1991 Published by Elsevier Inc.
