Manipulation of thrombus formation in the hamster cheek pouch with drugs that interact with PGI2 in vitro.
A single platelet thrombus was formed in an arteriole of the hamster cheek pouch by electrical stimulation followed by topical application of ADP. The sizes of the thrombi were continuously recorded with a photocell placed on a TV monitor screen and quantified by areas on the record. Repeated application of small doses of ADP (5-15 nmole/10 microliters) resulted in very reproducible formation of the thrombi, and the size of the thrombi was reduced dose-dependently by topical application of PGI2. Three drugs were tested in this model. Cyclooxygenase inhibitor (indomethacin 10 mg/kg, i.p.) increased the formation of thrombi, while a smaller dose (3 mg/kg) did not have any significant effect. This could be explained by inhibition of the generation of endogenous PGI2, since aggregation of hamster platelets by ADP was not inhibited by indomethacin in vitro. EG-626 (phthalazinol, a phosphodiesterase inhibitor) (300 mg/kg, i.p.) decreased the size of thrombus. AI-122 (1.0 mg/kg, i.p.), which has been proven to enhance PGI2 biosynthesis from isolated rat aortae, also decreased the formation. Thus, drugs such as EG-626 or AI-122 are quite promising as anti-thrombotic drugs.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D011464:Epoprostenol / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D009284:Naphthols / Q000494:pharmacology; D010793:Phthalazines; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology*
D009284:Naphthols; D010793:Phthalazines; D011453:Prostaglandins; C011329:phthalazinol; D000244:Adenosine Diphosphate; C035374:1-iodo-3-aminomethyl-5,6,7,8-tetrahydro-2-naphthol; D011464:Epoprostenol; D007213:Indomethacin