Pulmonary arterial hypertension (PAH) is associated with aberrant pulmonary
vascular remodeling that leads to increased pulmonary artery pressure, pulmonary vascular resistance, and
right ventricular dysfunction. There is now accumulating evidence that the renin-angiotensin-aldosterone system is activated and contributes to cardiopulmonary remodeling that occurs in PAH. Increased plasma and lung tissue levels of
angiotensin and
aldosterone have been detected in experimental models of PAH and shown to correlate with cardiopulmonary hemodynamics and pulmonary
vascular remodeling. These processes are abrogated by treatment with
angiotensin receptor or
mineralocorticoid receptor antagonists. At a cellular level,
angiotensin and
aldosterone activate
oxidant stress signaling pathways that decrease levels of bioavailable
nitric oxide, increase
inflammation, and promote cell proliferation, migration, extracellular matrix remodeling, and
fibrosis. Clinically, enhanced
renin-
angiotensin activity and elevated levels of
aldosterone have been detected in patients with PAH, which suggests a role for
angiotensin and
mineralocorticoid receptor antagonists in the treatment of PAH. This review will examine the current evidence linking renin-angiotensin-aldosterone system activation to PAH with an emphasis on the cellular and molecular mechanisms that are modulated by
aldosterone and may be of importance for the pathobiology of PAH.