Faculty Collaboration Database

A role for heterocellular coupling and EETs in dilation of rat cremaster arteries. Microcirculation 2006 Mar;13(2):119-30

Date

02/07/2006

Pubmed ID

16459325

DOI

10.1080/10739680500466400

Scopus ID

2-s2.0-32344437242 (requires institutional sign-in at Scopus site)   51 Citations

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.

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.

Author List

McSherry IN, Sandow SL, Campbell WB, Falck JR, Hill MA, Dora KA

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Animals
Arteries
Calcium
Calcium Signaling
Dose-Response Relationship, Drug
Endothelium, Vascular
Enzyme Inhibitors
Gap Junctions
Male
Muscle, Smooth, Vascular
Potassium Channels, Calcium-Activated
Rats
Rats, Wistar
Sodium-Potassium-Exchanging ATPase
Vasodilation
Vasodilator Agents