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

Abstract

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.