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CLINICAL STUDY

Atrial natriuretic peptide in severe primary and nonprimary pulmonary hypertension

Response to iloprost inhalation

^a Department of Internal Medicine II, Justus-Liebig-University, Giessen, Germany

Manuscript received December 15, 2000; revised manuscript received May 31, 2001, accepted June 19, 2001.

Reprint requests and correspondence: Dr. Horst Olschewski, Department of Internal Medicine II, Klinikstr. 36, 35392 Giessen, Germany
horst.olschewski{at}innere.med.uni-giessen.de

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.

Abbreviations and Acronyms   ANP = atrial natriuretic peptide   cGMP = cyclic guanosine monophosphate   CI = cardiac index   CO = cardiac output   COPD = chronic obstructive pulmonary disease   CT = computed tomography   eNOS = endothelial nitric oxide synthase   mPAP = mean pulmonary arterial pressure   mSAP = mean systemic arterial pressure   NPPH = nonprimary pulmonary hypertension   PAWP = pulmonary artery wedge pressure   PPH = primary pulmonary hypertension   PVR = pulmonary vascular resistance   RAP = right atrial pressure   RIA = radioimmunoassay   RV = right ventricle, right ventricular   RVEF = right ventricular ejection fraction   SvO2 = mixed venous oxygen saturation

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