Mechanisms of vasoconstriction induced by 9,11-epithio-11,12-methano-thromboxane A2 in the rabbit coronary artery.
The vasoconstrictor effects of 9,11-epithio-11,12-methano-thromboxane A2 (STA2) on smooth muscle strips of the rabbit coronary artery have been investigated in vitro. Right coronary artery (RCA) was more responsive to STA2 than either the left anterior descending or the circumflex coronary artery. On endothelium-denuded RCA strips, the sensitivity and responsiveness to STA2 were greater than observed on intact muscle strips. A thromboxane(Tx)-antagonist, (9,11), (11,12)-dideoxa-9 alpha, 11 alpha-dimethylmethano-11,12-methano-13,14-dihydro-13-aza-14-oxo-15 - cyclopenthyl-16,17,18,19,20-pethanol-15-epi-TxA2 (ONO-3708), inhibited the STA2-induced contraction, whereas atropine or prazosin had no effect. Nifedipine partly inhibited the STA2-induced contraction, one half of which was still evoked in Ca2+-free solution. When acetylcholine was applied prior to the application of STA2 in Ca2+-free solution, the STA2-vasoconstriction disappeared. In saponin-treated chemically skinned muscle strips, STA2 itself had no effect on either the pCa-tension relation or on the release of Ca2+ from intracellular stores. However, inositol 1,4,5-trisphosphate released Ca2+ from such stores, and 12-o-tetradecanoyl phorbol-13-acetate (TPA) and 1,2-diolein, activators of protein kinase C, enhanced the contraction induced by 0.3 microM Ca2+. It is concluded that STA2 acts on the TxA2 receptor and produces contraction due to an increase in both voltage- and agonist(receptor)-dependent Ca2+ influx. STA2 also releases Ca2+ from ACh- and caffeine-sensitive storage sites.
D000818:Animals; D001158:Arteries; D001285:Atropine / Q000494:pharmacology; D001696:Biomechanical Phenomena; D002118:Calcium / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004727:Endothelium / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction
D013928:Thromboxane A2; D001285:Atropine; C037866:STA 2; C049855:ONO 3708; D009543:Nifedipine; D002118:Calcium; D011224:Prazosin