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

Malarvannan Pannirselvam, Hong Ding, Todd J. Anderson, Christopher Triggle

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Endothelial dysfunction is considered as a major risk factor of cardiovascular complications of type I and type II diabetes. Our previous studies have demonstrated that endothelial dysfunction in the small mesenteric arteries from 12-16 week old type II 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 (BK Ca or Slo) channel, whereas the acetylcholine-induced, EDHF-mediated relaxation involves neither cytochrome P450 product nor hydrogen peroxide.

Original languageEnglish
Pages (from-to)98-107
Number of pages10
JournalEuropean Journal of Pharmacology
Volume551
Issue number1-3
DOIs
Publication statusPublished - 3 Dec 2006
Externally publishedYes

Fingerprint

Mesenteric Arteries
Endothelium
Bradykinin
Pharmacology
Acetylcholine
Charybdotoxin
Cytochrome P-450 Enzyme System
Apamin
Calcium-Activated Potassium Channels
Tetraethylammonium
Ouabain
Barium
Catalase
Type 2 Diabetes Mellitus
Hydrogen Peroxide
Potassium
Nitric Oxide
Calcium
Messenger RNA

Keywords

  • db/db mice
  • Endothelial dysfunction
  • Endothelium-derived hyperpolarizing factor
  • Epoxyeicosotrienoic acid
  • Potassium channels
  • Small mesenteric artery

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Pharmacological characteristics of endothelium-derived hyperpolarizing factor-mediated relaxation of small mesenteric arteries from db/db mice. / Pannirselvam, Malarvannan; Ding, Hong; Anderson, Todd J.; Triggle, Christopher.

In: European Journal of Pharmacology, Vol. 551, No. 1-3, 03.12.2006, p. 98-107.

Research output: Contribution to journalArticle

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