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Differential effects of diet-induced obesity on BKca β1-subunit expression and function in rat skeletal muscle arterioles and small cerebral arteries
Journal article   Peer reviewed

Differential effects of diet-induced obesity on BKca β1-subunit expression and function in rat skeletal muscle arterioles and small cerebral arteries

L Howitt, Shaun L Sandow, T Hilton Grayson, Z E Ellis, M J Morris and T V Murphy
American Journal of Physiology - Heart and Circulatory Physiology, Vol.301(1), pp.H29-H40
2011
url
https://doi.org/10.1152/ajpheart.00134.2011View
Published Version

Abstract

arteriolar remodeling large conductance calcium-activated potassium channel myogenic tone
Mechanisms underlying obesity-related vascular dysfunction are unclear. This study examined the effect of diet-induced obesity on expression and function of large conductance Ca2+-activated potassium channel (BKCa) 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 Ca α-subunit function or α -subunit protein or mRNA expression in vessels isolated from the cremaster muscle or middle-cerebral circulations. In contrast, BKCa β1-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 β1-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 BKCa antagonist iberiotoxin constricted both cremaster muscle and middlecerebral arterioles from control rats; this effect of iberiotoxin was abolished in cremaster muscle arteries only from obese rats. Dietinduced obesity has contrasting effects on BKCa function in different vascular beds, through differential effects on β 1-subunit expression. However, these alterations in BKCa function had little effect on overall myogenic tone, suggesting that the mechanisms controlling myogenic tone can be altered and compensate for altered BKCa expression and function. © 2011 the American Physiological Society.

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Cardiac & Cardiovascular Systems
Peripheral Vascular Disease
Physiology

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