Smooth muscle mediates circumferential conduction of hyperpolarization and relaxation to focal endothelial cell activation in large coronary arteries

Stavros Selemidis, Tom M Cocks

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Longitudinal conduction of endothelium-dependent vasodilatation is mediated by intercellular spread of hyperpolarization via gap junctions along the endothelium. If similar electrical signals from the endothelium conduct around the circumference of arteries via smooth muscle cells, then, both longitudinal and circumferential spread of such signals would make it possible for a wide annulus of a large blood vessel like an epicardial coronary artery to dilate to local stimuli. To examine this in vitro, we developed a dual-chambered organ bath in which both membrane potential and force are independently determined in endothelium-intact and -denuded regions of a single annulus of artery. Hyperpolarizations and relaxations to endothelium-dependent vasodilators like bradykinin (BK) and substance P in smooth muscle cells immediately beneath the local endothelium-intact region (local responses) are conducted via smooth muscle cells around the circumference of the artery. The local relaxation was partially inhibited by the nitric oxide synthase inhibitor, N (G)-nitro-L: -arginine (L: -NOARG), and subsequently abolished by further treatment with a combination of two characteristic inhibitors of endothelium-dependent hyperpolarization-the Ca(2+)-activated potassium channel (K(Ca)) channel inhibitors, apamin and charybdotoxin. The conducted hyperpolarizations and relaxations to BK were unaffected by L: -NOARG, but were abolished by apamin and charybdotoxin. In conclusion, these studies demonstrate for the first time that NO acts only as a local vasodilator, whereas endothelium-dependent hyperpolarization (EDH) causes local and remote vasodilatation in large coronary arteries. We propose that such a remote EDH-dependent signalling mechanism compensates for the loss of the local NO-dependent vasodilatation in diseased arteries.
Original languageEnglish
Pages (from-to)85 - 94
Number of pages10
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Issue number2
Publication statusPublished - 2007

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