Role of gap junctions and EETs in endothelium‐dependent hyperpolarization of porcine coronary artery
G Edwards, C Thollon, MJ Gardener… - British journal of …, 2000 - Wiley Online Library
G Edwards, C Thollon, MJ Gardener, M Feletou, JP Vilaine, PM Vanhoutte, AH Weston
British journal of pharmacology, 2000•Wiley Online LibraryThe effects of endothelium‐derived hyperpolarizing factor (EDHF: elicited using substance P
or bradykinin) were compared with those of 11, 12‐EET in pig coronary artery. Smooth
muscle cells were usually impaled with microelectrodes through the adventitial surface.
Substance P (100 nm) and 11, 12‐EET (11, 12‐epoxyeicosatrienoic acid; 3 μm)
hyperpolarized endothelial cells in intact arteries. These actions were unaffected by 100 nm
iberiotoxin but were abolished by charybdotoxin plus apamin (each 100 nm). Substance P …
or bradykinin) were compared with those of 11, 12‐EET in pig coronary artery. Smooth
muscle cells were usually impaled with microelectrodes through the adventitial surface.
Substance P (100 nm) and 11, 12‐EET (11, 12‐epoxyeicosatrienoic acid; 3 μm)
hyperpolarized endothelial cells in intact arteries. These actions were unaffected by 100 nm
iberiotoxin but were abolished by charybdotoxin plus apamin (each 100 nm). Substance P …
- The effects of endothelium‐derived hyperpolarizing factor (EDHF: elicited using substance P or bradykinin) were compared with those of 11,12‐EET in pig coronary artery. Smooth muscle cells were usually impaled with microelectrodes through the adventitial surface.
- Substance P (100 nM) and 11,12‐EET (11,12‐epoxyeicosatrienoic acid; 3 μM) hyperpolarized endothelial cells in intact arteries. These actions were unaffected by 100 nM iberiotoxin but were abolished by charybdotoxin plus apamin (each 100 nM).
- Substance P (100 nM) and bradykinin (30 nM) hyperpolarized intact artery smooth muscle; Substance P had no effect after endothelium removal.
- 11,12‐EET hyperpolarized de‐endothelialized vessels by 12.6±0.3 mV, an effect abolished by 100 nM iberiotoxin. 11,12‐EET hyperpolarized intact arteries by 18.6±0.8 mV, an action reduced by iberiotoxin, which was ineffective against substance P. Hyperpolarizations to 11,12‐EET and substance P were partially inhibited by 100 nM charybdotoxin and abolished by further addition of 100 nM apamin.
- 30 μM barium plus 500 nM ouabain depolarized intact artery smooth muscle but responses to substance P and bradykinin were unchanged. 500 μM gap 27 markedly reduced hyperpolarizations to substance P and bradykinin which were abolished in the additional presence of barium plus ouabain.
- Substance P‐induced hyperpolarizations of smooth muscle cells immediately below the internal elastic lamina were unaffected by gap 27, even in the presence of barium plus ouabain.
- In pig coronary artery, 11,12‐EET is not EDHF. Smooth muscle hyperpolarizations attributed to ‘EDHF’ are initiated by endothelial cell hyperpolarization involving charybdotoxin‐ (but not iberiotoxin) and apamin‐sensitive K+ channels. This may spread electrotonically via myoendothelial gap junctions but the involvement of an unknown endothelial factor cannot be excluded.
British Journal of Pharmacology (2000) 129, 1145–1154; doi:10.1038/sj.bjp.0703188
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