An endothelium-derived hyperpolarizing factor (EDHF) mediates a part of the vasodilatory action of bradykinin. A bioassay method was developed to investigate the properties of EDHF on bovine coronary arterial smooth muscle cells. Cannulated bovine coronary arteries with an intact endothelium that were treated with indomethacin and NG-nitro-L-arginine methyl ester served as the EDHF donor. The effect of the donor vessel perfusate was examined on a 240 pS single-channel calcium (Ca2+)-activated potassium (K+) current (KCa) and resting membrane potential in recipient coronary arterial smooth muscle cells. The open state probability (NPo) of the channel averaged 0.011 ± 0.003 during basal perfusate flow. After stimulation of the donor vessels with bradykinin (10–10–10–6 M), the perfusate induced a 1.2- to 5-fold increase in the NPo (n = 7, p < 0.001). This increase in channel activity was attenuated by either removing the endothelium of the donor arterial segment or upon inhibition of cytochrome P450 in the donor arterial segment with the combination of 17-octadecynoic acid and miconazole. The resting cell membrane averaged –60 ± 2 mV, and hyperpolarized to –69 ± 1.5 mV (n = 6, p < 0.05) in response to the perfusate following stimulation of the donor vessel with bradykinin. Addition of 14,15-epoxyeicosatrienoic acid mimicked the effects of the perfusate and increased the NPo of the KCa channel from 0.01 ± 0.001 to 0.05 ± 0.001. These findings suggest that bradykinin stimulates the release of a transferable endothelial factor that activates KCa channels and hyperpolarizes coronary arterial smooth muscle cell membranes. These findings support the hypothesis that coronary arteries release an EDHF which is a cytochrome P450 metabolite of arachidonic acid.
Prof. William B. Campbell, PhD
Medical College of Wisconsin, Department of Pharmacology & Toxicology
8701 Watertown Plank Road
Milwaukee, WI 53226 (USA)
Tel. +1 414 456 8267, Fax +1 414 456 6545, E-Mail email@example.com
Received: Received: November 26, 1997
Accepted after revision: March 3, 1998
Number of Print Pages : 11
Number of Figures : 7, Number of Tables : 0, Number of References : 34
Journal of Vascular Research
Founded 1964 as Angiologica by M. Comèl and L. Laszt (1964–1973) continued as Blood Vessels by J.A. Bevan (1974–1991)
Vol. 35, No. 4, Year 1998 (Cover Date: July-August 1998)
Journal Editor: M.J. Mulvany, Aarhus
ISSN: 1018–1172 (print), 1423–0135 (Online)
For additional information: http://www.karger.com/journals/jvr
Article / Publication Details
Published online: 8/7/1998
Issue release date: July–August 1998
Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0
ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)
For additional information: http://www.karger.com/JVR
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