Reversal of chronic hypoxia-induced alterations in pulmonary artery smooth muscle electromechanical coupling upon air breathing.
Cardiovasc Res
; 53(4): 1019-28, 2002 Mar.
Article
em En
| MEDLINE
| ID: mdl-11922912
ABSTRACT
OBJECTIVE:
Chronic hypoxia (CH) induces selective pulmonary hypertension which is accompanied by structural and functional alterations in the pulmonary vasculature. Little information is available on the regression of CH-induced functional alterations of pulmonary wall. In the present work, we investigated the reversal of CH-induced pulmonary hypertension with a special focus on alterations in the electrophysiological properties of pulmonary artery smooth muscle cells (PAMCs) after normoxia recovery.METHODS:
Rats were exposed to a hypobaric environment for 3 weeks (CH rats) and then subjected to a normoxic environment for 3 weeks (normoxia-recovery group) and compared with rats maintained in a normoxic environment (control rats). Electrophysiological properties of PAMCs were studied using conventional microelectrodes and patch-clamp technique.RESULTS:
CH rats exhibited a threefold increase in pulmonary blood pressure compared to control rats and this increase was fully reversed following 3 weeks of normoxia. PAMCs from CH rats were depolarised (about 20 mV), had an elevated calcium concentration and exhibited a hypersensitivity to 4-aminopyridine (4-AP) of membrane potential as well as the tone of arterial rings compared with tissues from control rats. Whole cell patch-clamp recordings indicated that voltage gated potassium channel currents I(Kv) and I(K(N)) were decreased in PAMCs from CH rats with a hyper sensitivity of I(K(N)) to 4-AP. CH-induced alterations in electrophysiological properties of PAMCs were also fully reversed after 3 weeks of normoxia recovery.CONCLUSIONS:
Both the increase in the pulmonary blood pressure and alterations in electrophysiological properties of PASMCs simultaneously reverse after normoxia recovery. This complete reversibility of all of the CH-induced pulmonary vascular alterations suggests that curative treatments for PAHT may now be designed aimed at targeting the very limited key factors implicated in hypoxia sensing.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
/
Hipertensão Pulmonar
/
Hipóxia
/
Músculo Liso Vascular
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
França