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

Malarvannan Pannirselvam, Hong Ding, Todd J. Anderson, Chris R. Triggle

Research output: Contribution to journalArticle

40 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 (BKCa 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

    Fingerprint

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this