Role of Ca(2+)-sensitive K(+) channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases.
Cardiovasc Res
; 60(2): 326-36, 2003 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-14613862
ABSTRACT
OBJECTIVE:
Clinically, the effect of chronic hypoxia (CH) in the pulmonary circulation alternates between phases of pulmonary artery hypertension (CH-PAHT) and normoxic normotensive remission (N-RE). Little information is available on the role of calcium-sensitive potassium channels (BK(Ca)) in both CH-PAHT and N-RE phases. In the present study, we investigated the effects of both CH and N-RE on BK(Ca) channels activity and their consequences on hypoxic pulmonary vasoconstriction (HPV).METHODS:
Using isolated ring preparation, the patch-clamp technique, RT-PCR and Western immunoblotting, we examined the role of the BK(Ca) channel in normoxic, CH-PAHT and N-RE rat pulmonary artery smooth muscle cells (PASMCs).RESULTS:
In intrapulmonary arterial rings, acute hypoxia induced contraction in control vessels, relaxation in the N-RE rats, and had no effect in CH-PAHT. The hypoxia-induced relaxation in the N-RE rat pulmonary arteries was abolished by iberiotoxin (IbTx), a specific BK(Ca) blocker. The IbTx-sensitive whole-cell K(Ca) channel current was reduced in CH-PAHT and increased in N-RE rat PASMCs. The BK(Ca) channel conductance and voltage sensitivity were not altered in CH and N-RE rat PASMCs, whereas its calcium sensitivity was decreased and increased in CH and N-RE rat PASMCs, respectively. Results of RT-PCR and Western blot analysis revealed a decrease in the mRNA and protein of the BK(Ca) alpha-subunit in CH, whereas no change at protein level was observed in the N-RE.CONCLUSION:
In rat PASMCs, CH and N-RE are associated with a down- and up-regulation of BK(Ca) activity, respectively, mainly due to modifications of its Ca(2+) sensitivity. This could explain the acute hypoxic pulmonary constriction and relaxation observed in CH and N-RE rats, respectively.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
/
Doença Pulmonar Obstrutiva Crônica
/
Canais de Potássio Cálcio-Ativados
/
Hipertensão Pulmonar
/
Músculo Liso Vascular
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
França