Differential participation of calcium-activated potassium channel in endothelium-dependent hyperpolarization-type relaxation in superior mesenteric arteries of spontaneously hypertensive rats

Can J Physiol Pharmacol. 2018 Aug;96(8):839-844. doi: 10.1139/cjpp-2017-0557. Epub 2018 Mar 20.

Abstract

The purpose of this study was to determine the relationship of KCa channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs. WKY). Treatment with large-conductance Ca2+-activated K+ channels (BKCa) inhibitor specifically attenuated relaxation in SHR, but not in WKY. Protein expression of IKCa and SKCa in the arteries did not differ between the 2 groups, whereas ratio of sloβ1 subunit to α subunit of BKCa was increased in SHR (vs. WKY). These results suggest that EDHF-mediated relaxations in superior mesenteric arteries are impaired in SHR, and utilize components of BKCa in addition to SKCa/IKCa channel activities, that the increased participation of BKCa may be attributable to alterations in α and sloβ1 subunit ratio, and that components unrelated to KCa activity may also contribute to the difference between SHR and WKY arteries.

Keywords: SHR; artère mésentérique supérieure; calcium-activated potassium channel; canal potassique activé par le calcium; endothelium-dependent hyperpolarization; hyperpolarisation dépendante de l’endothélium; hypertension; rat spontanément hypertendu; superior mesenteric artery.

MeSH terms

  • Acetylcholine / pharmacology
  • Action Potentials / physiology*
  • Animals
  • Biological Factors / metabolism
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiopathology*
  • Male
  • Mesenteric Artery, Superior / physiopathology*
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Calcium-Activated / metabolism*
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Vasodilation*

Substances

  • Biological Factors
  • Potassium Channel Blockers
  • Potassium Channels, Calcium-Activated
  • endothelium-dependent hyperpolarization factor
  • Acetylcholine