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Downregulation of the α2‐isoform of the Na,K‐pump inhibits EDHF‐like responses in rat mesenteric small arteries
Author(s) -
Aalkjaer Christian,
Nielsen Nina Moeller,
Matchkov Vladimir
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.853.4
Subject(s) - downregulation and upregulation , mesenteric arteries , gene isoform , chemistry , electrical impedance myography , vasodilation , endocrinology , medicine , apamin , acetylcholine , artery , potassium channel , biochemistry , gene
Oubain is known to inhibit vascular relaxation mediated by EDHF. Since oubain acts on several isoforms of the Na,K‐pump and can activate a signaling cascade in addition to inhibit ion‐translocation we investigated whether downregulation of the α2‐isoform of the Na,K‐pump affects the EDHF‐like response. The α2‐isoform of the Na,K‐pump was downregulated with siRNA in rat mesenteric small arteries and the functional effect assessed by isometric myography in arteries constricted with norepinephrine in a concentration providing 80–90% of maximal tone. Downregulation was confirmed at the RNA and protein level There was no difference in relaxation to acetylcholine between the downregulated and control arteries (maximal relaxation 71±10 and 80±15%, n=7, respectively). After inhibition of NOS and COX less relaxation was seen in downregulated arteries compared to control (36±11 and 78±16%, n=7, respectively, p<0.05). Addition of TRAM34 and apamin fully inhibited this relaxation (6±4 and 4±4%, respectively). The study demonstrated the importance of the α2‐isoform of the Na,K‐pump for relaxation via EDHF and strongly indicates that the effects of oubain on EDHF is mediated via this isoform of the Na,K‐pump.