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Alterations in KATP and KCa channel function in cerebral arteries of insulin-resistant rats.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2002 Dec; Vol. 283 (6), pp. H2472-7. Date of Electronic Publication: 2002 Aug 08. - Publication Year :
- 2002
-
Abstract
- We examined whether insulin resistance alters the function of ATP-dependent and Ca(2+)-activated K(+) channels (K(ATP) and K(Ca) channels, respectively) in pressurized isolated middle cerebral arteries (MCAs) from fructose-fed insulin-resistant (IR) and control rats. Blockade of K(Ca) channels with tetraethylammonium chloride (TEA, 2.5 mM) or iberiotoxin (IBTX, 0.1 microM) increased the spontaneously developed tone in control MCAs by 10.5 +/- 1.3% (n = 10) and 13.3 +/- 2.3% (n = 6), respectively. In the IR arteries, TEA induced similar constrictions (8.0 +/- 1.1%, n = 10), but IBTX constricted the IR arteries by only 3.1 +/- 0.9% (n = 8; P < 0.01). Bradykinin (BK)-induced endothelium-mediated relaxation was reduced in IR MCAs. Maximum relaxation to BK (10(-6) M) was 42 +/- 4% in control (n = 9) and 19 +/- 2% in IR (n = 10; P < 0.01) arteries. Pretreatment with TEA, IBTX, or the K(ATP) channel blocker glibenclamide (10 microM) inhibited relaxation to BK in control MCAs but did not alter dilation in IR arteries. Relaxation to the K(ATP) channel opener cromakalim was also diminished in IR MCAs. Maximum relaxation to cromakalim (10(-5) M) was 48 +/- 3% in control (n = 6) and 19 +/- 2% in IR arteries (n = 6; P < 0.01). These findings demonstrate that insulin resistance alters the function of K(ATP) and K(Ca) channels in isolated MCAs and affects the control of resting vascular tone and the mediation of dilator stimuli.
- Subjects :
- Animals
Bradykinin pharmacology
Cromakalim pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Fructose pharmacology
Hyperinsulinism metabolism
Hyperlipidemias metabolism
Hypertriglyceridemia blood
In Vitro Techniques
Lipoproteins, HDL blood
Male
Potassium Channel Blockers pharmacology
Rats
Rats, Sprague-Dawley
Vasoconstriction drug effects
Vasoconstriction physiology
Vasoconstrictor Agents pharmacology
Vasodilation drug effects
Vasodilation physiology
Vasodilator Agents pharmacology
Adenosine Triphosphate metabolism
Calcium metabolism
Cerebral Arteries metabolism
Insulin Resistance physiology
Potassium Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 283
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12388242
- Full Text :
- https://doi.org/10.1152/ajpheart.00516.2002