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

Howitt L, Sandow SL, Grayson TH, Ellis ZE, Morris MJ, Murphy TV. Differential effects of diet-induced obesity on BKCa beta(1)-subunit expression and function in rat skeletal muscle arterioles and small cerebral arteries. Am J Physiol Heart Circ Physiol 301: H29-H40, 2011. First published May 2, 2011; doi:10.1152/ajpheart.00134.2011.-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; similar to 30% energy from fat) for 16-20 wk were similar to 30% heavier than controls fed standard chow (similar to 13% fat). Obesity did not alter BKCa alpha-subunit function or alpha-subunit protein or mRNA expression in vessels isolated from the cremaster muscle or middle-cerebral circulations. In contrast, BKCa beta(1)-subunit protein expression and function were significantly reduced in cremaster muscle arterioles but increased in middle-cerebral arteries from obese animals. Immunohistochemistry showed alpha- and beta(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 BKCa 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 BKCa function in different vascular beds, through differential effects on beta(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.