On the relationship between the inhibition of thrombin stimulated aggregation and thromboxane formation in isolated platelets treated with beta-adrenoceptor blocking drugs.
Thromboxane B2 (TXB2) formation in isolated, thrombin-stimulated rat platelets was time dependent and appeared after 5 s of incubation. Beta-adrenoceptor blocking (BAB) drugs inhibited thrombin-stimulated TXB2 formation in the following rank order of potency: metipranolol approximately alprenolol approximately propranolol > oxprenolol > practolol. Atenolol was ineffective in inhibiting TXB2 production in stimulated platelets. The inhibition of thrombin-stimulated TXB2 formation by BAB drugs correlated with their inhibitory effect on thrombin-stimulated platelet aggregation, arachidonic acid liberation from membrane phospholipids and with their membrane fluidization. The higher was the liposolubility of the beta-adrenoceptor blocking drugs investigated, the higher was their inhibition of stimulated TXB2 formation. Hydrophilic, selective atenolol and practolol revealed slight or no inhibitory effect on stimulated thromboxane production.
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
R
R
Nosál
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V
Jancinová
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M
Petríková
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001262:Atenolol / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D014290:Metipranolol / Q000494:pharmacology; D010096:Oxprenolol / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011217:Practolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000096:biosynthesis*
D000319:Adrenergic beta-Antagonists; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D001262:Atenolol; D010096:Oxprenolol; D013928:Thromboxane A2; D000526:Alprenolol; D011433:Propranolol; D013917:Thrombin; D011217:Practolol; D014290:Metipranolol