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Role of Ca(2+)-sensitive K(+) channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases.
- Source :
-
Cardiovascular research [Cardiovasc Res] 2003 Nov 01; Vol. 60 (2), pp. 326-36. - Publication Year :
- 2003
-
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).<br />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).<br />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.<br />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.
- Subjects :
- Animals
Blotting, Western methods
Calcium metabolism
Hypertension, Pulmonary metabolism
Hypoxia
In Vitro Techniques
Male
Muscle, Smooth, Vascular metabolism
Patch-Clamp Techniques
Peptides pharmacology
Potassium Channel Blockers pharmacology
Potassium Channels, Calcium-Activated analysis
Potassium Channels, Calcium-Activated genetics
Pulmonary Artery metabolism
Pulmonary Disease, Chronic Obstructive metabolism
RNA, Messenger analysis
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Vasodilation drug effects
Hypertension, Pulmonary physiopathology
Muscle, Smooth, Vascular physiopathology
Potassium Channels, Calcium-Activated physiology
Pulmonary Artery physiopathology
Pulmonary Disease, Chronic Obstructive physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-6363
- Volume :
- 60
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cardiovascular research
- Publication Type :
- Academic Journal
- Accession number :
- 14613862
- Full Text :
- https://doi.org/10.1016/s0008-6363(03)00527-3