MilliporeSigma
  • Home
  • Search Results
  • Type 2 diabetes: increased expression and contribution of IKCa channels to vasodilation in small mesenteric arteries of ZDF rats.

Type 2 diabetes: increased expression and contribution of IKCa channels to vasodilation in small mesenteric arteries of ZDF rats.

American journal of physiology. Heart and circulatory physiology (2014-08-17)
Christian Schach, Markus Resch, Peter M Schmid, Guenter A Riegger, Dierk H Endemann
ABSTRACT

Impaired endothelial function, which is dysregulated in diabetes, also precedes hypertension. We hypothesized that in Type 2 diabetes, the impaired endothelium-dependent relaxation is due to a loss of endothelium-derived hyperpolarization (EDH) that is regulated by impaired ion channel function. Zucker diabetic fatty (ZDF), Zucker heterozygote, and homozygote lean control rats were used as the experimental models in our study. Third-order mesenteric arteries were dissected and mounted on a pressure myograph; mRNA was quantified by RT-PCR and channel proteins by Western blotting. Under nitric oxide (NO) synthase and cyclooxygenase inhibition, endothelial stimulation with ACh fully relaxes control but not diabetic arteries. In contrast, when small-conductance calcium-activated potassium (KCa) channels and intermediate- and large-conductance KCa (I/BKCa) are inhibited with apamin and charybdotoxin, NO is able to compensate for ACh-induced relaxation in control but not in diabetic vessels. After replacement of charybdotoxin with 1-[(2-chlorophenyl)diphenylmethyl]-(1)H-pyrazole (TRAM-34; IKCa inhibitor), ACh-induced relaxation in diabetic animals is attenuated. Specific inhibition with TRAM-34 or charybdotoxin attenuates ACh relaxation in diabetes. Stimulation with 1-ethyl-2-benzimidazolinone (IKCa activator) shows a reduced relaxation in diabetes. Activation of BKCa with 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-(2)H-benzimidazol-2-one NS619 leads to similar relaxations of control and diabetic arteries. RT-PCR and Western blot analysis demonstrate elevated mRNA and protein expression levels of IKCa in diabetes. Our results suggest that the compensatory effect of NO and EDH-associated, endothelium-dependent relaxation is reduced in ZDF rats. Specific blockade of IKCa with TRAM-34 reduces NO and EDH-type relaxation in diabetic rats, indicating an elevated contribution of IKCa in diabetic small mesenteric artery relaxation. This finding correlates with increased IKCa mRNA and protein expression in this vessel.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Magnesium sulfate, BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Apamin, from bee venom, ≥95% (HPLC)
Sigma-Aldrich
Apamin, synthetic, ≥97% (HPLC)
Sigma-Aldrich
Magnesium sulfate, ≥99.99% trace metals basis
Sigma-Aldrich
Sodium chloride, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
Sodium chloride, tablet
Sigma-Aldrich
Sodium acetate, powder, BioReagent, suitable for electrophoresis, suitable for cell culture, suitable for insect cell culture, ≥99%
Sigma-Aldrich
Sodium chloride solution, 5 M
Sigma-Aldrich
Sodium acetate, BioXtra, ≥99.0%
Sigma-Aldrich
Sodium chloride, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
Sodium acetate, meets USP testing specifications, anhydrous
Sigma-Aldrich
Sodium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
Sodium chloride, tested according to Ph. Eur.
Sigma-Aldrich
Sodium chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
Sodium acetate, anhydrous, for molecular biology, ≥99%
Sigma-Aldrich
Sodium chloride, meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%
Sigma-Aldrich
Sodium chloride solution, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
Sodium chloride solution, 0.9% in water, BioXtra, suitable for cell culture
Sigma-Aldrich
Magnesium sulfate solution, for molecular biology, 1.00 M±0.04 M
Sigma-Aldrich
Sodium chloride, 99.999% trace metals basis
Supelco
Sodium chloride, certified reference material for titrimetry, certified by BAM, ≥99.5%
Sigma-Aldrich
Sodium acetate solution, BioUltra, for molecular biology, ~3 M in H2O
Sigma-Aldrich
Sodium acetate, anhydrous, BioUltra, for luminescence, for molecular biology, ≥99.0% (NT)
Sigma-Aldrich
Sodium chloride solution, BioUltra, for molecular biology, ~5 M in H2O
Sigma-Aldrich
Sodium chloride solution, 0.85%
Supelco
Sodium acetate solution, NMR reference standard, 50 mM in D2O (99.9 atom % D), water 1 %, NMR tube size 3 mm × 8 in.
Sigma-Aldrich
Sodium chloride, AnhydroBeads, −10 mesh, 99.99% trace metals basis
Sigma-Aldrich
Sodium chloride, AnhydroBeads, −10 mesh, 99.999% trace metals basis
Sigma-Aldrich
Sodium Acetate Anhydrous, >99%, FCC, FG
Sigma-Aldrich
Sodium acetate, 99.995% trace metals basis