title: Reduction of large-conductance Ca²(+) -activated K(+) channel with compensatory increase of nitric oxide in insulin resistant rats.
abstract: Cardiovascular disease prevalence and mortality are both increased by insulin resistance, hypertension, and atherosclerosis. The large-conductance Ca(2+)-activated K(+) channel (BK(Ca)) plays a pivotal role in the diastolic function of vascular smooth muscle cells. However, the role of this channel in insulin resistance remains unknown. Male Sprague-Dawley rats were randomly divided into an insulin resistant group and control group. We investigated the BK(Ca) current and subunit expression in myocytes from aortas and mesenteric arteries by Western blot, real-time PCR and the whole-cell patch-clamp methods. BK(Ca) current was decreased in smooth muscle cells in insulin resistant rats, compared with that in control group. Peak BK(Ca) current at + 60 mV was significantly decreased after iberiotoxin (IBTX) perfusion at 100 nmol/L (64.2 ± 4.7 versus 20.3 ± 3.5% in thoracic aortas and 65.6 ± 6.2 versus 29.3 ± 3.9% in mesenteric arteries, both p < 0.01). However, there was no significant difference in BK(Ca) alpha subunit between the two groups, both at the level of mRNA and protein. BK(Ca) beta 1 subunit expression in aortas and mesenteric arteries from the insulin resistant group was lower than in those from control group. The plasma level of nitric oxide was higher in the insulin resistant group than in the control group. Our results demonstrated that the BK(Ca) channel is decreased both in macrovessels and microvessels in insulin resistant rats. These impairments may be related to the down-regulation of β1 subunit expression and compensatory increase in plasma nitric oxide levels.
authors.affiliation: Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China. lshjlshj@sina.com
authors.forename: Shangjian
authors.initials: S
authors.lastname: Li
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Deng
authors.forename: Liqiang
authors.initials: L
authors.lastname: Wei
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.forename: Wenting
authors.initials: W
authors.lastname: Ai
authors.forename: Xiling
authors.initials: X
authors.lastname: Shou
authors.forename: Xinyi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D009569:Nitric Oxide; C064719:iberiotoxin