A role for heterocellular coupling and EETs in dilation of rat cremaster arteries

Microcirculation. 2006 Mar;13(2):119-30. doi: 10.1080/10739680500466400.


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 IK(Ca) (1 microM 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 microM 17-ODYA or 10 microM 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 K(IR) (30 microM Ba2+) and Na+/K+-ATPase (10 microM 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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Arteries / physiology
  • Arteries / ultrastructure
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / physiology*
  • Endothelium, Vascular / ultrastructure
  • Enzyme Inhibitors / pharmacology
  • Gap Junctions / metabolism
  • Gap Junctions / ultrastructure
  • Male
  • Muscle, Smooth, Vascular / physiology*
  • Muscle, Smooth, Vascular / ultrastructure
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors
  • Potassium Channels, Calcium-Activated / metabolism*
  • Rats
  • Rats, Wistar
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Vasodilation / drug effects
  • Vasodilation / physiology*
  • Vasodilator Agents / pharmacology


  • Enzyme Inhibitors
  • Potassium Channels, Calcium-Activated
  • Vasodilator Agents
  • Sodium-Potassium-Exchanging ATPase
  • Acetylcholine
  • Calcium