ABSTRACT
<p><b>OBJECTIVE</b>To study the role of apelin in the prevention of pulmonary hypertension induced by hypoxia in rats.</p><p><b>METHODS</b>The animal model of hypoxic pulmonary hypertension was established by exposing the rats to isobaric hypoxic chamber for 4 weeks (8 h/d, 6 d/ w). Forty male Sprague-Dawley rats were randomly divided into control group (NC), hypoxic group(HH), hypoxic with low-dose apelin (5 nmol/(kg x d) group(LA) and high-dose apelin (10 nmol/(kg x d) (HA). [pGlu]apelin-13 was administered into the rats of apelin groups by mini-osmotic pump subcutaneously. The mean pulmonary arterial pressure(mPAP) and the mean carotid arterial pressure (mCAP) were measured by either right or left cardiac catheterization, and the weight ratio of right ventricule/left ventricule plus septum (RV/(LV + S)) were calculated. The Masson's trichrome stained lung specimens were examined by light microscope to examine the vessel wall area/total area (WA/TA), vessel cavity area/total area (CA/TA) and media thickness of pulmonary arterioles (PAMT). Meanwhile, the lung homogenates were assayed for the activity of supeeroxide dismutase (SOD) and the content of malondialdehyde (MDA).</p><p><b>RESULTS</b>(1) mPAP and RV/(LV + S) of HH group were significantly higher than those of NC group. mPAP of LA and HA groups were lower than those of HH group. The RV/(LV + S) of HA group was significantly lower than that of HH group, but there was no significant difference between HH group and LA group. (2) Masson's trichrome staining revealed that WA/TA and PAMT of HH group were higher than those of NC group. Administration of apelin significantly eliminated WA/TA and PAMT in LA and HA groups. (3) CA/TA of HH group was lower than that of NC group. Administration of apelin significantly elevated CA/TA in LA and HA groups. (4) The activity of SOD and content of MDA in HH group was, respectively, lower and higher than those in NC group. Apelin treatment increased the activity of SOD in LA and HA groups while decreased the content of MDA.</p><p><b>CONCLUSIONS</b>Apelin could play an important role in treatment of hypoxic pulmonary hypertension of rats and the mechanisms of protection were associated with vasodilation of pulmonary artery and inhibition of oxidative stress.</p>
Subject(s)
Animals , Male , Rats , Cardiotonic Agents , Pharmacology , Therapeutic Uses , Hypertension, Pulmonary , Hypoxia , Intercellular Signaling Peptides and Proteins , Pharmacology , Therapeutic Uses , Oxidative Stress , Pulmonary Artery , Rats, Sprague-Dawley , VasodilationABSTRACT
<p><b>AIM</b>To investigate the changes and probable roles of adrenomedullin2/intermedin (AIDM2/IMD), a novel micromolecular bioactive peptide, in the lungs of rats with chronic hypoxic pulmonary hypertension.</p><p><b>METHODS</b>Twenty male SD rats were randomly divided into normal control group (NC) and normobaric hypoxia group (4H). The protein levels of ADM and ADM2/IMD) in the plasma and lung were measured by radioimmunoassay and immunohistochemistry. The mRNA expressions of ADM, ADM2/IMD and their receptors C (RLR, RAMP1, RAMP2 and RAMP3 in the lung tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>(1) The rat model of chronic pulmonary hypertension was confirmed by the increased mean pulmonary arterial pressure (mPAP) and weight ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] in 4H group compared to NC group. (2) The concentrations of ADM in the plasma and lung homogenate of 4H group were 2.3 and 3.2 folds of NC group, respectively (all P < 0.01). The levels of ADM2/IMD were higher 89.6% and 45.0% in the plasma and lung homogenate of 4H group than those of NC group (respectively, P < 0.01, P < 0.05). (3) The mRNA expressions of ADM2/IMD and ADM in the lung of 4H group were up-regulated (respectively, P < 0.01, P < 0.05 vs. NC group). The expressions of CRLR and RAMP1 mRNAs were down-regulated (all P < 0.01 vs. NC group), while the levels of RAMP2 and RAMP3 mRNAs were no significant difference between the two groups. (4) The strong ADM2/IMD immunostaining was detected in the endothelial and adventitial cells of the rat pulmonary arteriole.</p><p><b>CONCLUSION</b>ADM2/IMD, like its paralog ADM, might be closely related to the chronic hypoxic pulmonary hypertension in rats. The disorders of the gene expression and/or the synthesis and metabolism of ADM2/IMD and its receptor CRLR/RAMP1 possibly take part in the pathogenesis of chronic hypoxic pulmonary hypertension in rats.</p>