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Reduction of large-conductance Ca2+-activated K+ channel with compensatory increase of nitric oxide in insulin resistant rats
Cardiovascular disease prevalence and mortality are both increased by insulin resistance, hypertension, and atherosclerosis. The large‐conductance Ca2+‐activated K+ channel (BKCa) plays a pivotal role in the diastolic function of vascular smooth muscle cells. However, the role of this channel in ins...
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Published in: | Diabetes/metabolism research and reviews 2011-07, Vol.27 (5), p.461-469 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | Cardiovascular disease prevalence and mortality are both increased by insulin resistance, hypertension, and atherosclerosis. The large‐conductance Ca2+‐activated K+ channel (BKCa) 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 BKCa current and subunit expression in myocytes from aortas and mesenteric arteries by Western blot, real‐time PCR and the whole‐cell patch‐clamp methods. BKCa current was decreased in smooth muscle cells in insulin resistant rats, compared with that in control group. Peak BKCa 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 BKCa alpha subunit between the two groups, both at the level of mRNA and protein. BKCa 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 BKCa 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. Copyright © 2011 John Wiley & Sons, Ltd. |
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ISSN: | 1520-7552 1520-7560 |
DOI: | 10.1002/dmrr.1196 |