Spreading dilatation in rat mesenteric arteries associated with calcium-independent endothelial cell hyperpolarization

• Published in: The Journal of physiology Vol. 556; no. 3; pp. 887 - 903
• Main Authors: Takano, Hiromichi, Dora, Kim A., Spitaler, Michaela M., Garland, Chris J.
• Format: Journal Article
• Language: English
• Published: 9600 Garsington Road , Oxford , OX4 2DQ , UK The Physiological Society 01-05-2004; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: Acetylcholine - pharmacology; Aniline Compounds - chemistry; Animals; Barium - pharmacology; Calcium - metabolism; Cromakalim - pharmacology; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - physiology; Fluorescent Dyes - chemistry; Glyburide - pharmacology; In Vitro Techniques; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; Microscopy, Fluorescence; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Organic Chemicals; Patch-Clamp Techniques; Phenylephrine - pharmacology; Propidium - chemistry; Rats; Rats, Wistar; Research Papers; Vasodilation - physiology; Xanthenes - chemistry
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2003.060343

Both ACh and levcromakalim evoke smooth muscle cell hyperpolarization and associated relaxation in rat mesenteric resistance
arteries. We investigated if they could evoke conducted vasodilatation along isolated arteries, whether this reflected spreading
hyperpolarization and the possible mechanism involved. Focal micropipette application of either ACh, to stimulate endothelial
cell muscarinic receptors, or levcromakalim, to activate smooth muscle K ATP channels, each evoked a local dilatation (88 ± 14%, n = 6 and 92 ± 6% reversal of phenylephrine-induced tone, n = 11, respectively) that rapidly spread upstream (at 1.5 mm 46 ± 19%, n = 6 and 57 ± 13%, n = 9) to dilate the entire isolated artery. The local dilatation to ACh was associated with a rise in endothelial cell [Ca 2+ ] i ( F / F t = 0 = 1.22 ± 0.33, n = 14) which did not spread beyond 0.5 mm ( F / F t = 0 = 1.01 ± 0.01, n = 14), while the local dilatation to levcromakalim was not associated with any change in endothelial cell [Ca 2+ ] i . In contrast, ACh and levcromakalim both stimulated local (12.7 ± 1.2 mV, n = 10 and 13.5 ± 4.7 mV, n = 10) and spreading (at 2 mm: 3.0 ± 1.1 mV, n = 5 and 4.1 ± 0.7 mV, n = 5) smooth muscle hyperpolarization. The spread of hyperpolarization could be prevented by cutting the artery, so was not
due to a diffusible agent. Both the spreading dilatation and hyperpolarization were endothelium dependent. The injection of
propidium iodide into either endothelial or smooth muscle cells revealed extensive dye coupling between the endothelial cells,
but limited coupling between the smooth muscle cells. Some evidence for heterocellular spread of dye was also evident. Together,
these data show that vasodilatation can spread over significant distances in mesenteric resistance arteries, and suggest this
reflects an effective coupling between the endothelial cells to facilitate [Ca 2+ ] i -independent spread of hyperpolarization.