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.
Nosál
R
R
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Jancinová
V
V
Petríková
M
M
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