The significant role of the endothelium-derived relaxing factor nitric oxide (NO) and the endothelium-derived vasoconstrictor peptide endothelin-1 (ET-1) in pathogenesis of pulmonary arterial hypertension (PAH) is accepted. It is know that synthesis of endothelin is inhibited by NO, and that NO plays a significant role in vascular tone regulation during hypoxia.

Objective: 

The aim of our study was to investigate the effects of endothelin converting enzyme inhibitor (ECEI) - PP36 (Pozdnev et al.1998) on NOx production with urine and endothelin-1 plasma levels in Wistar rats with hypoxia induced PAH (hPAH).

Methods: 

Animals were tested on tolerance to hypoxia and were divided in 2 groups: low hypoxia tolerance (LHT) and high hypoxia tolerance (HHT). hPAH was induced by the adaptation to hypobaric hypoxia (10% O₂) during 2 weeks. PP36 (1.4 mg/kg) was added to the drinking water during 2 weeks too. Urine NOx and ET-1 and angiotensin plasma levels were measured.

Results: 

hPAH increased production of NOx with urine in rats with HHT (67.910.2 vs. 24.24.4) and decreased it in rats with LHT (16.30.4 vs. 24.24.4). ECEI increased urine NOx in rats with hPAH and HHT (107.112.1 vs. 24.24.4) and showed no effect on rats with LHT (15.90.5 vs. 24.24.4). Plasma levels of ET-1 in rats with hPAH and HHT was increased (0.630.06 vs. 0.540.01).and 0.810.01 vs. 0.540.01 in rats with LHT. ECEI decreased ET-1 plasma level (0.420.02 vs. 0.520.01) in rats with hPAH both HHT and LHT.

Conclusion: 

This data shows that chronic treatment with ECE inhibitor significantly reduces endothelin-1 plasma level in rats with hPAH. Changes in NOx production due to hPAH correlated with animals' tolerance to hypoxia.