Objective: To investigate the alteration of plasma and lung tissue homogenate urotensin II (U-II), nitric oxide (NO) and C-type natriuretic peptide (CNP) levels in rats with hypoxia-induced pulmonary hypertension (HPH) and to study the role of these factors and oxygen treatment in the development of HPH.
Methods: Thirty male Wistar rats were randomly divided into three groups: a control group, a group with hypoxia for 14 days and a group with oxygen treatment after hypoxia for 14 days, 10 rats per group. Mean pulmonary arterial pressure (mPAP), mean systematic arterial pressure (mSAP) and right ventriculo hypertrophy index (RVHI) were measured. The plasma levels of U-II, NO, CNP, and the lung tissue homogenate levels of U-II and CNP were measured. The structure of the pulmonary arteries was examined using optical microscope. The microstructure and ultrastructure changes in pulmonary small arteries were examined using electron microscope.
Results: The mPAP and RVHI in the hypoxia group [(34.1 +/- 2.8) mm Hg, 0.43 +/- 0.11] were higher than those in the control group [(18.9 +/- 2.0) mm Hg, 0.28 +/- 0.04, all P < 0.01]. The plasma levels of U-II, NO, and CNP [(4.4 +/- 0.9) pg/ml, (20.8 +/- 7.0) micromol/L, (6.6 +/- 1.2) pg/ml], and the lung tissue homogenate levels of U-II and CNP [(6.3 +/- 0.5), (1.89 +/- 0.43) pg/ml] in the hypoxia group were higher than those in the control group [(0.9 +/- 0.4) pg/ml, (13.2 +/- 2.0) micromol/L, (4.0 +/- 0.6) pg/ml, (2.6 +/- 0.5) pg/ml, (0.69 +/- 0.21) pg/ml, respectively, all P < 0.01]. Compared with the hypoxia group, the mPAP, the plasma levels of U-II, NO, and CNP, and the lung tissue homogenate levels of U-II and CNP in the oxygen treatment group [(31.4 +/- 2.0) mm Hg, (2.1 +/- 0.7) pg/ml, (14.8 +/- 1.7) micromol/L, (4.4 +/- 0.7) pg/ml; (3.5 +/- 0.8) pg/ml, (0.74 +/- 0.17) pg/ml, respectively] were significantly decreased (all P < 0.01). The pulmonary vessel morphology changes of the oxygen treatment group were ameliorated.
Conclusions: U-II, NO and CNP are involved in the pathophysiologic process of HPH. Imbalance of these factors may be partially responsible for the development of the disease.