Role of gap junctions in the responses to EDHF in rat and guinea‐pig small arteries

• Published in: British journal of pharmacology Vol. 128; no. 8; pp. 1788 - 1794
• Main Authors: Edwards, G, Félétou, M, Gardener, M J, Thollon, C, Vanhoutte, P M, Weston, A H
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.1999; Nature Publishing
• Subjects: 1‐EBIO; Acetylcholine - pharmacology; Animals; Anti-Ulcer Agents - pharmacology; Arteries - drug effects; Arteries - physiology; Biological and medical sciences; Biological Factors - pharmacology; carbenoxolone; Carbenoxolone - pharmacology; Cardiovascular system; carotid artery; Connexins - pharmacology; EDHF; endothelial cell; gap 27; gap junctions; Gap Junctions - drug effects; Gap Junctions - physiology; Guinea Pigs; hepatic artery; Male; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; mesenteric artery; Muscle, Smooth, Vascular - drug effects; Pharmacology. Drug treatments; Potassium - pharmacology; Potassium Chloride - pharmacology; Rats; Vascular wall; Vasodilator Agents - pharmacology; Hepatic artery; Animal model; Internal carotid; Endothelial cell; Rat; Rodentia; Biological activity; Gap junction; Vertebrata; Mesenteric artery; Mammalia; Guinea pig; Animal; Membrane potential; Mechanism of action; Hyperpolarization
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703009

In guinea‐pig internal carotid arteries with an intact endothelium, acetylcholine (10 μM) and levcromakalim (10 μM) each hyperpolarized the smooth muscle whereas a 5 mM elevation of extracellular K+ was without effect. Incubation of the carotid artery with the gap junction inhibitors carbenoxolone (100 μM) or gap 27 (500 μM) essentially abolished the hyperpolarization to acetylcholine but it was without effect on that to levcromakalim. Carbenoxolone had no effect on the acetylcholine‐induced endothelial cell hyperpolarization but inhibited the smooth muscle hyperpolarization induced by the endothelial cell K+ channel opener, 1‐ethyl‐2‐benzimidazolinone (600 μM). In rat hepatic and mesenteric arteries with endothelium, carbenoxolone (100 or 500 μM) depolarized the smooth muscle but did not modify hyperpolarizations induced by KCl or levcromakalim. In the mesenteric (but not the hepatic) artery, the acetylcholine‐induced hyperpolarization was inhibited by carbenoxolone. Phenylephrine (1 μM) depolarized the smooth muscle cells of intact hepatic and mesenteric arteries, an effect enhanced by carbenoxolone. Gap 27 did not have a depolarizing action. In the presence of phenylephrine, acetylcholine‐induced hyperpolarization of both hepatic and mesenteric artery myocytes was partially inhibited by each of the gap junction inhibitors. Collectively, the data suggest that gap junctions play some role in the EDHF (endothelium‐derived hyperpolarizing factor) response in rat hepatic and mesenteric arteries. However, in the guinea‐pig internal carotid artery, electrotonic propagation of endothelial cell hyperpolarizations via gap junctions may be the sole mechanism underlying the response previously attributed to EDHF. British Journal of Pharmacology (1999) 128, 1788–1794; doi:10.1038/sj.bjp.0703009