Synergism between prostanoids and other vasoactive agents
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AbstractBackground. Prostaglandin E-2 is usually considered to be a vasodilator, but some vascular beds respond with weak vasoconstriction mediated by prostanoid EP3-receptors. We have used the guinea pig isolated thoracic aorta to examine the nature of the synergism between the EP3 agonist sulprostone and other vasoactive agents. Methods: Muscle tension was recorded from endothelium-denuded rings of aorta suspended in conventional organ baths. Indomethacin and the TP-receptor antagonist GR 32191 were usually present. Results: Sulprostone (0.1-300 nM) showed two profiles: low-responder preparations (maximum response = 15-35% of 100 nM U-46619 response) were insensitive to the L-type Ca2+ blocker nifedipine, whereas high-responders (maximum = 35-70%) showed a nifedipine-sensitive component at higher sulprostone concentrations only. Charybdotoxin (CTX), a blocker of large-conductance Ca2+-activated K+ channels (BKCa), slightly enhanced threshold sulprostone responses and markedly enhanced larger responses; the enhancements were abolished by nifedipine. In contrast, threshold sulprostone responses were dramatically enhanced in the presence of established small contractions to phenylephrine (alpha(1)-adrenoceptor agonist), U-46619 (TP agonist), cyclopiazonic acid (sarcoplasmic Ca2+ pump inhibitor), and 4-aminopyridine (4-AP, K-v channel blocker). Nifedipine had no effect on enhancements of threshold sulprostone responses, and partially inhibited the enhancements of larger responses. Conclusions: BKCa channel activation appears to increase progressively as sulprostone-induced contraction increases. CTX removes this "BKCa brake," thereby providing an "L-type channel" Ca2+ flux to prime the EP3-receptor-driven Ca2+-sensitization mechanism (via Rho-kinase activation, unpublished observations). In contrast, the other agents, including 4-AP, direct a non-L-type channel source of Ca2+ to the calmodulin-myosin light chain arm.
All Author(s) ListJones RL, Shum WWC, Gurney AM
Name of Conference1st International Symposium on Cardiovascular Science
Start Date of Conference23/11/2001
End Date of Conference24/11/2001
Place of ConferenceHONG KONG
Journal nameJournal of Cardiac Surgery
Volume Number17
Issue Number5
Pages436 - 438
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesCardiac & Cardiovascular Systems; CARDIAC & CARDIOVASCULAR SYSTEMS; Cardiovascular System & Cardiology; Surgery; SURGERY

Last updated on 2020-21-11 at 01:29