RT Journal Article
SR Electronic
T1 Increased renin-angiotensin-aldosteron system activity in lungs of patients with idiopathic pulmonary arterial hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p1516
VO 38
IS Suppl 55
A1 Frances S. de Man
A1 Christophe Guignabert
A1 Ly Tu
A1 Charlene Francois
A1 Gerard Simmoneau
A1 Elie Fadel
A1 Marc Humbert
A1 Anton Vonk-Noordegraaf
A1 Saadia Eddahibi
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p1516.abstract
AB Studies have reported over-activation of the sympathetic nerve system (SNS) in patients with idiopathic Pulmonary Arterial Hypertension (iPAH). Since the Renin-Angiotensin-Aldosteron-System (RAAS) is closely related to SNS and the lungs are the major site for angiotensin 2 formation, we hypothesized that RAAS-activity is increased in iPAH.Pulmonary endothelial cell (P-EC) cultures were generated from lung specimens of iPAH-patients (n=5) and controls (n=5) to assess angiotensin converting enzyme (ACE) activity (Fig. 1A). We determined angiotensin 2 production upon incubation with angiotensin 1 alone and in combination with ACE-inhibitor enalapril. Subsequently, protein levels of the angiotensin 2 receptor type 1 (AT1R) and tyrosine kinase SRC-activity (downstream target of AT1R) were evaluated in pulmonary arteries (PA) homogenates.P-EC of iPAH-patients produced significantly more angiotensin 2 upon angiotensin 1 incubation, compared to control. Interestingly, enalapril normalized angiotensin 2 production (Fig. 1B). In addition, pulmonary arteries of iPAH-patients exhibited increased AT1R expression and accentuated SRC-activity (Fig. 1C,D)Figure 1Conclusion: This study demonstrates increased RAAS-activity in lungs of iPAH-patients, illustrated by elevated ACE-activity and AT1R signalling. Future studies will focus on the effects of chronic inhibition of RAAS on pulmonary vascular remodelling in iPAH.