A Role for Heterocellular Coupling and EETs in Dilation of Rat Cremaster Arteries

Objective: The authors probed endothelium-dependent dilation and endothelial cell Ca2 + 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 Ca2 + were monitored using confocal microscopy, and arterial ultrastructure was determined using electron microscopy. Results: Acetylcholine (ACh) stimulated elevations and oscillations in endothelial cell Ca2 +, and concentration-dependently dilated arteries with myogenic tone. NO-independent dilation was blocked by 35 mM K+. Combined IKCa (1 μ M TRAM-34) and SKCa (100 nM apamin) blockade partially inhibited NO-independent relaxations, with residual relaxations sensitive to BKCa 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 Ca2 +. 15 mM K+ evoked dilation sensitive to inhibition of KIR (30 μ M Ba2 +) 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 Ca2 + stimulate SKCa and IKCa channels, leading to hyperpolarization and dilation, likely due to electrical coupling. In addition, a component was unmasked following SKCa and IKCa blockade, attributable to activation of BKCa channels by cytochrome P-450 metabolites.