Faculty Collaboration Database

Peroxynitrite inhibits Ca2+-activated K+ channel activity in smooth muscle of human coronary arterioles. Circ Res 2002 Nov 29;91(11):1070-6

Date

11/29/2002

Pubmed ID

12456494

DOI

10.1161/01.res.0000046003.14031.98

Scopus ID

2-s2.0-0037195428 (requires institutional sign-in at Scopus site)   141 Citations

Abstract

We examined the hypothesis that ONOO-, a product of the interaction between superoxide (O2*-) and nitric oxide (NO), inhibits calcium-activated K+ (KCa) channel activity in vascular smooth muscle cells (VSMCs) of human coronary arterioles (HCAs), thereby reducing hyperpolarization-mediated vasodilation. HCAs were dissected from right atrial appendages. The interaction of ONOO- with microvessels was determined by immunohistochemistry using a nitrotyrosine antibody. Strong staining was observed in arteries exposed to authentic ONOO- or to sodium nitroprusside (SNP)+xanthine (XA)+xanthine oxidase (XO). Dilation to 10(-8) mol/L bradykinin (BK) was abolished in vessels exposed to ONOO- (-2.5+/-8%; P<0.05) but not DC-ONOO- (65+/-8%). Reduced dilation to BK was also observed after application of XO and SNP. Dilation to NS1619 (KCa channel opener) was reduced in endothelial denuded arterioles treated with ONOO-. In isolated VSMCs, whole-cell peak K+ current density was reduced by ONOO- (control 65+/-15 pA/pF; ONOO- 42+/-9 pA/pF; P<0.05). Iberiotoxin had no further effect on whole-cell K+ current. In inside-out patches, ONOO- but not DC-ONOO- decreased open state probability (NP(o)) of KCa channel by 50+/-12%. O2*- generated by XA+XO had no effect on BK-induced dilation and NP(o) of KCa channels. These results suggest that ONOO-, but not O2*-, inhibits KCa channel activity in VSMCs possibly by a direct effect. This mechanism may contribute to impaired EDHF-mediated dilation in conditions such as ischemia/reperfusion where increased activity of NO synthase occurs in the presence of excess of O2*-.

Author List

Liu Y, Terata K, Chai Q, Li H, Kleinman LH, Gutterman DD

Author

David Gutterman MD Emeritus Professor in the Medicine department at Medical College of Wisconsin

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

Animals
Arterioles
Coronary Vessels
Female
Humans
Immunohistochemistry
In Vitro Techniques
Male
Membrane Potentials
Microscopy, Video
Middle Aged
Muscle, Smooth, Vascular
Patch-Clamp Techniques
Peptides
Peroxynitrous Acid
Potassium
Potassium Channel Blockers
Potassium Channels, Calcium-Activated
Rats
Rats, Sprague-Dawley
Tyrosine
Vasodilation
Vasodilator Agents