Document Detail

KCa3.1 channel downregulation and impaired EDH-type relaxation in pulmonary arteries from chronic hypoxic rats.
MedLine Citation:
PMID:  23243147     Owner:  NLM     Status:  Publisher    
Calcium-activated potassium channels of small (KCa2, SK) and intermediate (KCa3.1, IK) conductance are involved in endothelium-dependent relaxation of pulmonary arteries. We hypothesized that KCa2 and KCa3.1 function and expression increase as a compensatory mechanism to counteract hypoxia-induced pulmonary hypertension in rats. For functional studies, pulmonary arteries were mounted in microvascular myographs for isometric tension recordings. KCa channel expression was evaluated by immunoblotting and quantitative PCR. Although acetylcholine (ACh) induced similar relaxations, ACh relaxations were abolished by the combined inhibition of nitric oxide synthase (L-nitro-arginine, L-NOARG), cyclooxygenase (indomethacin), and soluble guanylate cyclase (ODQ) in pulmonary arteries from hypoxic rats, whereas 20±6% (n=8) maximum relaxation to ACh persisted in arteries from normoxic rats. Inhibiting Na(+)/K(+) ATPase with ouabain or blocking KCa2 and KCa3.1 channels reduced the persisting ACh relaxation. A novel KCa2 and KCa3.1 channel activator, NS4591, induced concentration- and endothelium-dependent relaxations, which were markedly reduced in the presence of L-NOARG and indomethacin in arteries from chronic hypoxic rats compared with arteries from normoxic rats. KCa2.3 and KCa3.1 mRNA levels were unaltered, whereas KCa2.3 protein expression was upregulated and KCa3.1 protein expression was downregulated in pulmonary arteries from rats exposed to hypoxia. In conclusion, endothelium-dependent relaxation was conserved in pulmonary arteries from chronic hypoxic rats, while endothelium-derived hyperpolarization (EDH)-type relaxation was impaired in chronic hypoxic pulmonary small arteries despite upregulation of KCa2.3 channels. Since impaired EDH-type relaxation was accompanied by KCa3.1 channel protein downregulation, these findings suggest that KCa3.1 channels are important for the maintenance of EDH-type relaxation.
Christel Kroigaard; Olga Kudryavtseva; Thomas Dalsgaard; Christine Wandall-Frostholm; Søren-Peter Olesen; Ulf Simonsen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-13
Journal Detail:
Title:  Experimental physiology     Volume:  -     ISSN:  1469-445X     ISO Abbreviation:  Exp. Physiol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1 Aarhus University;
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