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HIGHLIGHTED TOPICS
Skeletal and Cardiac Muscle Blood Flow
The John B. Pierce Laboratory, New Haven 06519; and Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520
Submitted 4 February 2004 ; accepted in final form 25 May 2004
Functional hyperemia requires the coordination of smooth muscle cell relaxation along and between branches of the arteriolar network. Vasodilation is conducted from cell to cell along the arteriolar wall through gap junction channels composed of connexin protein subunits. Within skeletal muscle, it is unclear whether arteriolar endothelium, smooth muscle, or both cell layers provide the cellular pathway for conduction. Furthermore, the constitutive profile of connexin expression within the microcirculation is unknown. We tested the hypothesis that conducted vasodilation and connexin expression are intrinsic to the endothelium of arterioles (17 ± 1 µm diameter) that supply the skeletal muscle fibers in the cremaster of anesthetized C57BL/6 mice. ACh delivered to an arteriole (500 ms, 1-µA pulse; 1-µm micropipette) produced local dilation of 17 ± 1 µm; conducted vasodilation observed 1 mm upstream was 9 ± 1 µm (n = 5). After light-dye treatment to selectively disrupt endothelium (250-µm segment centered 500 µm upstream, confirmed by loss of local response to ACh while constriction to phenylephrine and dilation to sodium nitroprusside remained intact), we found that conducted vasodilation was nearly abolished (2 ± 1 µm; P < 0.05). Whole-mount immunohistochemistry for connexins revealed punctate labeling at borders of arteriolar endothelial cells, with connexin40 and connexin37 in all branches and connexin43 only in the largest branches. Immunoreactivity for connexins was not apparent in smooth muscle or in capillary or venular endothelium, despite robust immunolabeling for 
-actin and platelet endothelial cell adhesion molecule-1, respectively. We conclude that vasodilation is conducted along the endothelium of mouse skeletal muscle arterioles and that connexin40 and connexin37 are the primary connexins forming gap junction channels between arteriolar endothelial cells.
microcirculation; muscle blood flow; gap junctions
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