Item request has been placed!
×
Item request cannot be made.
×
Processing Request
Targeting endothelial K Ca channels in vivo restores arterial and endothelial function in type 2 diabetic rats.
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
- Additional Information
- Source:
Publisher: W.B. Saunders Country of Publication: United States NLM ID: 0375267 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-8600 (Electronic) Linking ISSN: 00260495 NLM ISO Abbreviation: Metabolism Subsets: MEDLINE
- Publication Information:
Publication: Philadelphia, PA : W.B. Saunders
Original Publication: New York, Grune & Stratton.
- Subject Terms:
- Abstract:
Objective: This study tested the hypothesis that administration of the KCa channel activator SKA-31 restores endothelium-dependent vasodilation in vivo in Type 2 Diabetic (T2D) rats.
Background: Acute treatment of isolated resistance arteries from T2D rats and humans with SKA-31 significantly improved endothelium-dependent vasodilation. However, it is unknown whether these in situ actions translate to intact vascular beds in vivo.
Methods: Male Sprague Dawley (SD) and T2D Goto-Kakizaki (GK) rats (26-32 weeks of age) were injected intraperitoneally with either drug vehicle or 10 mg/kg SKA-31. Doppler ultrasound imaging was used to record reactive hyperemia/flow-mediated dilation (FMD) in the femoral artery following release of an occlusion cuff on the distal hind limb, along with diameter changes in the left main coronary artery in response to inhaled isoflurane (2 % → 5 %).
Results: Vehicle treated SD rats exhibited a robust and reversible FMD response, the magnitude and time course of which did not differ in SD rats treated with SKA-31. In contrast, only a weak FMD response was observed in vehicle-treated T2D GK rats, whereas prior SKA-31 administration restored FMD to the level observed in control SD rats. Exposure of SD rats to 5 % isoflurane caused robust coronary artery dilation, which was not altered by prior treatment with SKA-31. In T2D GK rats, 5 % isoflurane inhalation alone did not increase coronary artery diameter, however, a strong vasodilatory response was observed following SKA-31 treatment. SKA-31 administration did not modify intrinsic heart rate responses in either protocol.
Conclusions: Enhancement of KCa channel activity in vivo restores endothelium-dependent vasodilation in T2D rats that exhibit peripheral endothelial dysfunction.
Competing Interests: Declaration of competing interest The authors declare that no conflicts of interest exist and have no financial interests associated with the present study.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Contributed Indexing:
Keywords: Coronary artery; Endothelial dysfunction; Flow-mediated dilation; Type 2 diabetes; Vasodilation
- Accession Number:
0 (naphtho(1,2-d)thiazol-2-ylamine)
0 (Benzothiazoles)
- Publication Date:
Date Created: 20240820 Date Completed: 20240911 Latest Revision: 20240912
- Publication Date:
20240913
- Accession Number:
10.1016/j.metabol.2024.156001
- Accession Number:
39163925
No Comments.