title: Differential effects of diet-induced obesity on BKCa {beta}1-subunit expression and function in rat skeletal muscle arterioles and small cerebral arteries.
abstract: Mechanisms underlying obesity-related vascular dysfunction are unclear. This study examined the effect of diet-induced obesity on expression and function of large conductance Ca(2+)-activated potassium channel (BK(Ca)) in rat pressurized small resistance vessels with myogenic tone. Male Sprague-Dawley rats fed a cafeteria-style high fat diet (HFD; ∼30% energy from fat) for 16-20 wk were ∼30% heavier than controls fed standard chow (∼13% fat). Obesity did not alter BK(Ca) α-subunit function or α-subunit protein or mRNA expression in vessels isolated from the cremaster muscle or middle-cerebral circulations. In contrast, BK(Ca) β(1)-subunit protein expression and function were significantly reduced in cremaster muscle arterioles but increased in middle-cerebral arteries from obese animals. Immunohistochemistry showed α- and β(1)-subunits were present exclusively in the smooth muscle of both vessels. Cremaster muscle arterioles from obese animals showed significantly increased medial thickness, and media-to-lumen ratio and pressurized arterioles showed increased myogenic tone at 30 mmHg, but not at 50-120 mmHg. Myogenic tone was not affected by obesity in middle-cerebral arteries. The BK(Ca) antagonist iberiotoxin constricted both cremaster muscle and middle-cerebral arterioles from control rats; this effect of iberiotoxin was abolished in cremaster muscle arteries only from obese rats. Diet-induced obesity has contrasting effects on BK(Ca) function in different vascular beds, through differential effects on β(1)-subunit expression. However, these alterations in BK(Ca) function had little effect on overall myogenic tone, suggesting that the mechanisms controlling myogenic tone can be altered and compensate for altered BK(Ca) expression and function.
authors.affiliation: Dept. of Physiology, School of Medical Sciences, Univ. of New South Wales, Sydney, NSW 2052 Australia. lauren.howitt5@gmail.com
authors.forename: Lauren
authors.initials: L
authors.lastname: Howitt
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Sandow
authors.forename: T Hilton
authors.initials: TH
authors.lastname: Grayson
authors.forename: Zoe E
authors.initials: ZE
authors.lastname: Ellis
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism*; D015153:Blotting, Western; D002536:Cerebral Arteries / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D002149:Energy Intake / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006946:Hyperinsulinism / Q000209:etiology / Q000503:physiopathology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007150:Immunohistochemistry; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D020738:Leptin / Q000097:blood; D008297:Male; D008854:Microscopy, Electron; D009129:Muscle Tonus / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D015221:Potassium Channels / Q000819:agonists / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015430:Weight Gain / Q000502:physiology
chemical_list: D004041:Dietary Fats; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D020738:Leptin; D015221:Potassium Channels