Premium
A Role for Heterocellular Coupling and EETs in Dilation of Rat Cremaster Arteries
Author(s) -
MCSHERRY IAIN N.,
SANDOW SHAUN L.,
CAMPBELL WILLIAM B.,
FALCK JOHN R.,
HILL MICHAEL A.,
DORA KIM A.
Publication year - 2006
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680500466400
Subject(s) - iberiotoxin , hyperpolarization (physics) , chemistry , biophysics , endothelium , vasodilation , gap junction , cremaster muscle , acetylcholine , endocrinology , arteriole , anatomy , medicine , microcirculation , biology , intracellular , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy
Objective: The authors probed endothelium‐dependent dilation and endothelial cell Ca 2 + handling in myogenically active resistance arteries. Methods: First‐order arteries were removed from rat cremaster muscles, cannulated, and pressurized (75 mmHg). Vessel diameter and endothelial cell Ca 2 + were monitored using confocal microscopy, and arterial ultrastructure was determined using electron microscopy. Results: Acetylcholine (ACh) stimulated elevations and oscillations in endothelial cell Ca 2 + , and concentration‐dependently dilated arteries with myogenic tone. NO‐independent dilation was blocked by 35 mM K + . Combined IK Ca (1 μ M TRAM‐34) and SK Ca (100 nM apamin) blockade partially inhibited NO‐independent relaxations, with residual relaxations sensitive to BK Ca or cytochrome P‐450 inhibition (100 nM iberiotoxin, and 20 μ M 17‐ODYA or 10 μ M MS‐PPOH). 11,12‐EET stimulated iberiotoxin‐sensitive dilation, but did not affect endothelial cell Ca 2 + . 15 mM K + evoked dilation sensitive to inhibition of K IR (30 μ M Ba 2 + ) and Na + /K + ‐ATPase (10 μ M ouabain), whereas these blockers did not affect ACh‐mediated dilations. Homo‐ and heterocellular gap junctions were identified in radial sections through arteries. Conclusion: These data suggest that rises in endothelial cell Ca 2 + stimulate SK Ca and IK Ca channels, leading to hyperpolarization and dilation, likely due to electrical coupling. In addition, a component was unmasked following SK Ca and IK Ca blockade, attributable to activation of BK Ca channels by cytochrome P‐450 metabolites.