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Sébastien Bonnet, Eric Dubuis, Christophe Vandier, Stéphanie Martin, Roger Marthan, Jean-Pierre Savineau, Reversal of chronic hypoxia-induced alterations in pulmonary artery smooth muscle electromechanical coupling upon air breathing, Cardiovascular Research, Volume 53, Issue 4, March 2002, Pages 1019–1028, https://doi.org/10.1016/S0008-6363(01)00548-X
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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 IKv and IK(N) were decreased in PAMCs from CH rats with a hyper sensitivity of IK(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.
