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Circulation Research. 2000;87:1048-1054

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(Circulation Research. 2000;87:1048.)
© 2000 American Heart Association, Inc.


Integrative Physiology

Integrated Ca2+ Signaling Between Smooth Muscle and Endothelium of Resistance Vessels

Yasuaki Yashiro, Brian R. Duling

From the First Department of Physiology (Y.Y.), Shinshu University School of Medicine, Matsumoto, Japan, and Department of Molecular Physiology and Biological Physics (B.R.D.), University of Virginia Health Sciences Center, Charlottesville, Va.

Correspondence to Dr Brian R. Duling, Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, PO Box 800736, Charlottesville, VA 22908-0736. E-mail brd{at}virginia.edu

Abstract—Cell-cell communication in the arteriolar wall was examined using the Ca2+-sensitive indicator fura-2 and the Ca2+ buffer BAPTA as means of measuring and buffering cellular Ca2+. The experiments focused on the role of endothelial cell [Ca2+]i in modulating phenylephrine (PE)-induced contractions in in vitro arterioles of the hamster cremaster. Fura-2-AM and BAPTA-AM were applied intraluminally to accomplish endothelium-specific loading. PE was applied to short segments of arterioles using pressure-pulse ejection from a micropipette. Under control conditions at the site of stimulation, PE elicited a strong vasoconstriction preceded by an increase in endothelial cell [Ca2+]i. A very small biphasic conducted response was observed at sites upstream from the stimulation site. BAPTA sharply reduced the measured Ca2+ response in the endothelium. This was associated with an enhanced local contractile response. In addition, the biphasic conducted response was converted into a strong conducted vasoconstriction. PE caused an initial rise in smooth muscle [Ca2+]i at the stimulated site, which was followed by a rapid decrease below baseline. Endothelial cell loading of BAPTA had minimal effect on the initial [Ca2+]i peak but eliminated the secondary decrease in smooth muscle [Ca2+]i. Intraluminal application of charybdotoxin plus apamin mimicked the change in vasomotor state induced by BAPTA. These data lead us to hypothesize that, after smooth muscle stimulation, intercellular Ca2+ signaling between smooth muscle and endothelium causes a secondary rise in endothelial cell Ca2+, which triggers a hyperpolarizing event and initiates a conducted vasodilation. We conclude that smooth muscle and endothelium operate as a functional unit in these vessels.


Key Words: phenylephrine • gap junctions • endothelium • [Ca2+]i • hyperpolarization




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