title: Alterations in KATP and KCa channel function in cerebral arteries of insulin-resistant rats.
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.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA. berdos@wfubmc.edu
authors.forename: Benedek
authors.initials: B
authors.lastname: Erdös
authors.forename: Allison W
authors.initials: AW
authors.lastname: Miller
authors.forename: David W
authors.initials: DW
authors.lastname: Busija
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002536:Cerebral Arteries / Q000378:metabolism*; D019806:Cromakalim / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000494:pharmacology; D006946:Hyperinsulinism / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000097:blood; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D008075:Lipoproteins, HDL; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D005632:Fructose; D000255:Adenosine Triphosphate; D001920:Bradykinin; D002118:Calcium