Atrial natriuretic peptide in severe primary and nonprimary pulmonary hypertension : Response to iloprost inhalation

OBJECTIVES The goal of this study was to assess atrial natriuretic peptide (ANP) levels during inhalation of iloprost in severe primary (PPH) and nonprimary pulmonary hypertension (NPPH). BACKGROUND The ANP system is activated in pulmonary hypertension and may help protect from right ventricular (RV) decompensation. It is unknown if ANP regulation is the same in severe PPH and NPPH and if the dynamic regulation is intact in a highly activated ANP system. METHODS In 11 patients with PPH and seven patients with NPPH, right heart catheter investigations were performed. Pulmonary and systemic artery ANP and cyclic guanosine monophosphate (cGMP) levels as well as hemodynamics were measured before and after iloprost inhalation. RESULTS The baseline hemodynamics of patients with PPH and patients with NPPH were comparable (mean pulmonary artery pressure [mPAP]: 61 ± 5 mm Hg vs. 52 ± 5 mm Hg, pulmonary vascular resistance [PVR]: 1,504 ± 153 dyne·s·cm−5 vs. 1,219 ± 270 dyne·s·cm−5. Atrial natriuretic peptide and cGMP levels were increased about tenfold and fivefold compared with controls in both PPH and NPPH. Iloprost inhalation significantly decreased mPAP (−9.1 ± 2.5 mm Hg vs. −7.9 ± 1.5 mm Hg), PVR (−453 ± 103 dyne·s·cm−5 vs. −381 ± 114 dyne·s·cm−5), ANP (−99 ± 63 pg/ml vs. −108 ± 47 pg/ml) and cGMP (−4.6 ± 0.9 nM vs. −4.2 ± 1.6 nM). Baseline ANP including all patients significantly correlated with PVR, right atrial pressure, cardiac index, RV ejection fraction, mixed venous oxygen saturation and cGMP. CONCLUSIONS The ANP system is highly activated in patients with severe PPH and NPPH. Atrial natriuretic peptide levels are significantly correlated with parameters of RV function and pre- and afterload. Iloprost inhalation causes a rapid decrease in ANP and cGMP in parallel with pulmonary vasodilation and hemodynamic improvement.