Prostacyclin release from the coronary vascular wall by vasoactive substances.
Which vasoactive substances that are synthesized in vivo could induce the release of a sufficient amount of prostacyclin (PGI2) to inhibit platelet aggregation from the vascular wall was investigated in the isolated dog heart perfused by a modified method of Langendorff. Infusion of 5 microM bradykinin or 25 u/ml crude thrombin into the heart for 30 sec resulted in the transient appearance of inhibitory activity of platelet aggregation. The inhibitory activity was stable at alkaline pH but unstable at acidic pH and thermolabile. The appearance of the inhibitory activity was prevented by treatment of the coronary vessel with 30 microM indomethacin or 1 mM tranylcypromine. These results indicated that the inhibitory activity was caused by PGI2. When 25 microM acetylcholine, 25 microM noradrenaline, 25 microM isoproterenol, 10 microM adenosine triphosphate (ATP), 5 microM adenosine, 1 microM angiotensin II, 25 microM histamine or 1 microM serotonin was infused for 30 sec, no inhibitory activity of platelet aggregation was observed. Bradykinin (5 X 10(-9) approximately 5 X 10(-6) M) and purified thrombin (1 X 10(-9) approximately 1 X 10(-7) M) induced a dose-dependent release of PGI2 which was assayed using a radioimmunoassay for 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha).
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D000804:Angiotensin II; D012701:Serotonin; D006632:Histamine; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D013917:Thrombin; D000241:Adenosine; D007545:Isoproterenol; D001920:Bradykinin