Mechanism of action of carbocyclic thromboxane A2 and its interaction with prostaglandin I2 and verapamil in isolated arteries.
Carbocyclic thromboxane A2 (10(-9) to 10(-7) M) produced a concentration-dependent contraction of helical strips of dog cerebral, coronary, mesenteric, renal, and femoral arteries and of monkey cerebral, coronary, and mesenteric arteries. Contraction induced by low concentrations of carbocyclic thromboxane A2 tended to be greater in cerebral arterial strips. Even after 60 minutes of exposure to Ca++-free media, approximately one-half of the contractile response of dog cerebral and mesenteric arteries to 10(-8) M carbocyclic thromboxane A2 was retained. The contractile response was attenuated by diphloretin phosphate, a prostaglandin antagonist, and was potentiated by aspirin. In dog cerebral arterial strips contracted with carbocyclic thromboxane, the relaxant response to prostaglandin I2 was less than the response seen in mesenteric and coronary arteries, whereas, in contrast, the response to verapamil was greater in cerebral arteries. Concentration-relaxation curves for papaverine did differ appreciably. It may be concluded that contractions induced by carbocyclic thromboxane are associated with the release of Ca++ from intracellular storage sites and, in addition, the increase in transmembrane Ca++ influx. Greater susceptibility of cerebral arteries to verapamil may indicate that the Ca++ antagonist is of use to relieve the persistent contraction of cerebroarterial smooth muscle. Prostaglandin I2 appears to counteract effectively the action of potent vasoconstrictors, such as thromboxane A2 and its carbocyclic analog, in various vascular beds.
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D002536:Cerebral Arteries / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D008251:Macaca; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D013931:Thromboxanes / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D011453:Prostaglandins; D013931:Thromboxanes; C024587:thromboxane A2, carbocyclic; D013928:Thromboxane A2; D014700:Verapamil; D011464:Epoprostenol