Modulation of ion channels in pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular hypertrophy, right heart failure and ultimately to death. PAH is a disease of small pulmonary arteries inducing vascular narrowing leading to a progressive increase in pulmonary vascular resistance. The therapeutic means that improve PAH are still very limited and are too often restricted to heart/lungs transplantation. Numerous forms of pulmonary hypertension exist. Although it is still unclear as to all types of PAH share a common pathogenesis, it is generally admitted that pulmonary vasoconstriction and remodelling of the arterial wall are key events. In this review, we discuss pulmonary artery smooth muscle cells (PASMC) ion channels implication in both phenomena and we examine whether variations in expression and/or the activity of these channels can contribute to the development of PAH with special attention to K(+), Cl(-) and voltage- and non voltage-activated Ca(2+) channels. For each family of ion channels, we describe their implication in the control of both membrane potential and resting cytosolic calcium concentration which are key parameters of PASMC in PAH. We also provide evidence for an implication of these channels in not only vasoconstriction but also proliferation and/or decreased apoptosis of PASMC, phenomena which contribute to remodelling of pulmonary arterial wall. In this respect, PAH may be considered as form of vascular "channelopathy". Finally, we present examples of some substances acting on ion channels and thus potentially constituting innovative therapeutic approaches of PAH.
Guibert
Christelle
C
Université Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux, France.
Marthan
Roger
R
Savineau
Jean-Pierre
JP
D000959:Antihypertensive Agents / Q000494:pharmacology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism*; D007473:Ion Channels / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000959:Antihypertensive Agents; D007473:Ion Channels