Mechanism of coronary vasoconstriction induced by carbocyclic thromboxane A2.
The mechanism of carbocyclic thromboxane A2 (CTA2) vasoconstriction was studied in thoracic aortic strips and isolated perfused cat coronary arteries. CTA2, a stable thromboxane analog, produced coronary constriction at 50 pg/ml or greater. At constant flow, 5 ng/ml CTA2 increased perfusion pressure 40 +/- 4 mmHg. The calcium antagonist nifedipine reduced CTA2-induced vasoconstriction by 8% at 1 ng/ml (NS), 22% at 10 ng/ml (NS), 65% at 100 ng/ml (P less than 0.01), and 75% at 1,000 ng/ml (P less than 0.005). Other calcium antagonists also significantly reduced CTA2-induced coronary constriction. Inhibition of vasoconstriction by calcium antagonists was not due to direct thromboxane-receptor antagonism, inasmuch as nifedipine did not prevent CTA2-induced contraction in cat aortas, vessels that are not dependent on external calcium for contraction. Reducing external Ca2+ concentration to 0.63 mM significantly reduced coronary constriction over most of the CTA2 concentration-response range. Phentolamine (1-50 micrograms/ml), phenoxybenzamine (1-100 micrograms/ml), and saralasin (0.1-10 micrograms/ml) were all without significant effect on CTA2-induced coronary constriction. The results indicate that the mechanism of thromboxane coronary vasoconstriction is by a specific thromboxane receptor that is dependent on an inward calcium flux. The data also suggest that the efficacy of calcium antagonists in coronary vasospasm may be related to their ability to noncompetitively inhibit thromboxane-induced vasoconstriction.
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology*; D002415:Cats; D003331:Coronary Vessels / Q000502:physiology*; D005260:Female; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011945:Receptors, Angiotensin / Q000502:physiology; D013928:Thromboxane A2 / Q000494:pharmacology*; D013931:Thromboxanes / Q000494:pharmacology*; D014661:Vasoconstriction; D014700:Verapamil / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011945:Receptors, Angiotensin; D013931:Thromboxanes; D013928:Thromboxane A2; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium