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REPORTS
1The John B. Pierce Laboratory, 2Department of Cellular and Molecular Physiology, 3Department of Biomedical Engineering, and 4Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut; 5Department of Medical Pharmacology and Physiology, University of Missouri-Columbia; and 6Dalton Cardiovascular Research Center, Columbia, Missouri
Submitted 8 June 2006 ; accepted in final form 7 November 2006
An increase in tissue blood flow requires relaxation of smooth muscle cells along entire branches of the resistance vasculature. Whereas the spread of hyperpolarization along the endothelium can coordinate smooth muscle cell relaxation, complementary signaling events have been implicated in the conduction of vasodilation. We tested the hypothesis that Ca2+ waves propagate from cell to cell along the endothelium of feed arteries exhibiting spontaneous vasomotor tone. Feed arteries of the hamster retractor muscle were isolated, pressurized to 75 mmHg at 37°C, and developed myogenic tone spontaneously. Smooth muscle cells and endothelial cells were loaded with the Ca2+ indicator Fluo-4. An acetylcholine stimulus was delivered locally using microiontophoresis (1-µm pipette tip, 1 µA, 1 s), and Ca2+ signaling within and along respective cell layers was determined using laser-scanning confocal microscopy. Acetylcholine triggered an increase in intracellular Ca2+ concentration ([Ca2+]i) of endothelial cells at the site of stimulation that preceded two distinct events: 1) a rapid synchronous decrease in smooth muscle [Ca2+]i along the entire vessel and 2) an ensuing Ca2+ wave that propagated bidirectionally along the endothelium at 
111 µm/s for distances exceeding 1 mm. Maximal dilation of vessels with either nifedipine (1 µM) or sodium nitroprusside (SNP, 100 µM) reduced the distance that Ca2+ waves traveled to 300 µm (P < 0.05). Thus Ca2+ waves propagate along the endothelium of resistance vessels with vasomotor tone, and this signaling pathway is compromised during maximal dilation with nifedipine or SNP.
blood flow; calcium imaging; conducted vasodilation; microcirculation; myogenic tone
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