Further investigations into the endothelium-dependent hyperpolarizing effects of bradykinin and substance P in porcine coronary artery

G. Edwards, M. Félétou, M. J. Gardener, C. D. Glen, G. R. Richards, P. M. Vanhoutte, A. H. Weston

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    1. In porcine coronary arteries, smooth muscle hyperpolarizations produced by the nitric oxide donor, NOR-1, and the prostacyclin analogue, iloprost, were compared with those induced by substance P and bradykinin and attributed to the endothelium-derived hyperpolarizing factor (EDHF). 2. In the presence of 300 μM L-nitroarginine and 10 μM indomethacin, iloprost-induced hyperpolarizations were partially inhibited by 10 μM glibenclamide whereas those to NOR-1, substance P and bradykinin were unaffected. 3. Hyperpolarizations produced by maximally-effective concentrations of NOR-1 and NS1619 were identical (to -65 mV). They were significantly less than those generated by either substance P or bradykinin (to approximately -80 mV) and were abolished by iberiotoxin 100 nM, a concentration which had essentially no effect on responses to substance P or bradykinin. 4. Incubation of segments of intact arteries for 16-22 h in bicarbonate-buffered Krebs solution had little effect on EDHF responses to substance P or bradykinin. In contrast, after incubation for this period of time in HEPES-buffered Tyrode solution or Krebs containing 10 mM HEPES the EDHF response to substance P was abolished and that to bradykinin was markedly reduced, The residual bradykinin-induced hyperpolarization following incubation in Tyrode solution was inhibited by iberiotoxin and by 10 μM 17-octadecynoic acid. 5. We conclude that substance P activates only the EDHF pathway in the presence of nitric oxide synthase and cyclo-oxygenase inhibitors. Incubation in HEPES-buffered Tyrode solution abolishes the EDHF responses to substance P and bradykinin to reveal an additional hyperpolarizing mechanism, associated with the opening of K + channels, activated only by bradykinin.
    Original languageEnglish
    Pages (from-to)1145-1153
    Number of pages8
    JournalBritish Journal of Pharmacology
    Issue number7
    Publication statusPublished - 2001


    • Bradykinin
    • EDHF
    • Gap junctions
    • HEPES
    • Hyperpolarization
    • Iberiotoxin
    • Nitric oxide donor
    • Porcine coronary artery
    • Prostacyclin
    • Substance P


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