title: A role for heterocellular coupling and EETs in dilation of rat cremaster arteries.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Bath, Bath, United Kingdom.
authors.forename: Iain N
authors.initials: IN
authors.lastname: McSherry
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Sandow
authors.forename: William B
authors.initials: WB
authors.lastname: Campbell
authors.forename: John R
authors.initials: JR
authors.lastname: Falck
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hill
authors.forename: Kim A
authors.initials: KA
authors.lastname: Dora
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000502:physiology / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology* / Q000648:ultrastructure; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D024681:Potassium Channels, Calcium-Activated; D014665:Vasodilator Agents; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D002118:Calcium