Journal article
Vascular expression of inducible nitric oxide synthase is associated with activation of Ca(++)-dependent K+ channels
The Journal of pharmacology and experimental therapeutics, Vol.279(3), pp.1514-1519
12/1996
DOI: 10.1016/S0022-3565(25)21313-1
PMID: 8968377
Abstract
We tested the hypothesis that expression of inducible nitric oxide synthase (NO-synthase) in response to endotoxin (lipopolysaccharide) produces activation of potassium channels. Contraction of the rat thoracic aorta in response to phenylephrine was measured in vitro after treatment in vivo for 15 hr with vehicle (control) or lipopolysaccharide (10 mg/kg i.p.). Impaired contraction in response to phenylephrine was used as an index of inducible NO-synthase expression, and activation of potassium channels was examined with specific inhibitors. Contraction in response to 10(-5) M phenylephrine (expressed as a percentage of contraction in response to 85 mM KCI) was markedly impaired in lipopolysaccharide-treated rats, compared with control (15 +/- 5% vs. 131 +/- 10%, P < .05, mean +/- S.E.). Expression of inducible NO-synthase mRNA in the vessel wall in lipopolysaccharide-treated rats was confirmed using reverse transcription-polymerase chain reaction. Contraction of the aorta in lipopolysaccharide-treated rats was restored to normal by 0.3 mM aminoguanidine (an inhibitor of inducible NO-synthase). Contraction of the aorta in response to phenylephrine, which was inhibited by lipopolysaccharide, was not affected by glibenclamide (an inhibitor of ATP-sensitive potassium channels) but was increased 2-fold (P < .05) by iberiotoxin (50 nM), an inhibitor of Ca(+2)-dependent potassium channels. Relaxation of the aorta in response to sodium nitroprusside, an exogenous donor of nitric oxide, and 8-bromo-cyclic GMP was also inhibited by iberiotoxin. These findings suggest that nitric oxide produced by vascular expression of inducible NO-synthase activates calcium-dependent potassium channels and that this mechanism may contribute to impaired vasoconstrictor responses during sepsis.
Details
- Title: Subtitle
- Vascular expression of inducible nitric oxide synthase is associated with activation of Ca(++)-dependent K+ channels
- Creators
- Hisao Taguchi - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USADonald D HeistadYi ChuC. David RiosHiroaki OoboshiFrank M Faraci
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.279(3), pp.1514-1519
- Publisher
- United States
- DOI
- 10.1016/S0022-3565(25)21313-1
- PMID
- 8968377
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Grant note
- NS24621 / NINDS NIH HHS HL38901 / NHLBI NIH HHS HL16066 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/1996
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040545702771
Metrics
13 Record Views