Pharmacological characteristics of endothelium-derived hyperpolarizing factor-mediated relaxation of small mesenteric arteries from db/db mice

Pannirselvam, M, Ding, H, Anderson, T and Triggle, C 2006, 'Pharmacological characteristics of endothelium-derived hyperpolarizing factor-mediated relaxation of small mesenteric arteries from db/db mice', European Journal of Pharmacology, vol. 551, pp. 98-107.


Document type: Journal Article
Collection: Journal Articles

Title Pharmacological characteristics of endothelium-derived hyperpolarizing factor-mediated relaxation of small mesenteric arteries from db/db mice
Author(s) Pannirselvam, M
Ding, H
Anderson, T
Triggle, C
Year 2006
Journal name European Journal of Pharmacology
Volume number 551
Start page 98
End page 107
Total pages 10
Publisher Elsevier Science
Abstract Endothelial dysfunction is considered as a major risk factor of cardiovascular complications of type I and type 11 diabetes. Our previous studies have demonstrated that endothelial dysfunction in the small mesenteric arteries from 12-16 week old type 11 diabetic mice was associated with decreased bio-availability of nitric oxide whereas endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation was preserved. The objective of the present study was to characterize EDHF-mediated relaxations of small mesenteric arteries from db/db mice. A depolarizing concentration of KCl or tetraethylammonium (TEA, 10 mM) significantly inhibited the EDHF-mediated relaxation to acetylcholine and bradykinin in small mesenteric arteries from both db/+ and db/db mice. Charybdotoxin or iberiotoxin alone and a combination of ouabain and barium significantly reduced the maximal relaxation to acetylcholine in small mesenteric arteries from db/db mice and charybdotoxin or iberiotoxin either alone or in combination with apamin reduced the sensitivity to the EDHF-mediated component of the relaxation response to bradykinin. 17-octadecynoic acid, but not catalase, significantly reduced the sensitivity to EDHF-mediated responses to bradykinin in db/db mice; 17-octadecynoic acid had no effect on acetylcholine-mediated relaxations. No differences were, however, detected for mRNA expression levels of calcium-activated potassium channels or connexins 37, 40, 43 and 45. Collectively, these data suggest that bradykinin-induced, EDHF-dependent relaxation in small mesenteric arteries from db/db mice is mediated via cytochrome P450 product that activates the large conductance calcium-activated potassium (BKCa or Slo) channel, whereas the acetylcholine-induced, EDHF-mediated relaxation involves neither cytochrome P450 product nor hydrogen peroxide.
Subject Basic Pharmacology
Keyword(s) Porcine Coronary-Arteries
Nitric-Oxide Synthase
Induced Diabetic-Rats
Natriuretic Peptide
Hydrogen-Peroxide
Dependent Hyperpolarization
Epoxyeicosatrienoic Acids
Resistance Vessels
Oxidative Stress
Cell Dysfunction
DOI - identifier 10.1016/j.ejphar.2006.08.086
Copyright notice © 2006 Elsevier B.V. All rights reserved.
ISSN 0014-2999
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