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

Publisher Website
Google Scholar
Abstract
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). 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. 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. 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. 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. British Journal of Pharmacology (2001) 133, 1145–1153; doi:10.1038/sj.bjp.0704157

This publication has 41 references indexed in Scilit: