Abstract：OBJECTIVE: To study the changes and significance of serum hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and calcium (Ca2+) levels in neonates with hypoxic pulmonary hypertension (HPH). METHODS: Seventy-five neonates with HPH (29 mild, 25 moderate and 21 severe) and 22 hospitalized neonates with non-HPH (control group) were enrolled. Pulmonary artery systolic blood pressure (PASP) was measured by bedside echocardiography within 24 hrs after birth. Serum levels of HIF-1α and ET-1 were measured using ELASA. Serum Ca2+ concentrations were measured with ion selective electrode. RESULTS: Serum levels of HIF-1α and ET-1 in the HPH group increased significantly compared with those in the control group (P<0.01), and were positively related with PASP (Rhif-1α=0.75, P<0.01; Ret-1=0.56，P<0.05). Serum Ca2+ levels in neonates with severe HPH were significantly lower than those in the control group (P<0.05). There were no correlation between serum Ca2+ levels and PASP. CONCLUSIONS: Serum HIF-1α and ET-1 levels are positively related with PASP in neonates with HPH, suggesting that serum HIF-1α and ET-1 may be involved in the occurrence of neonatal HPH. Serum Ca2+ levels are reduced in severe neonates with HPH, suggesting that serum Ca2+ may play a role in the occurrence of severe HPH.
［1］Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T, et al. Cooperative interaction of hypoxia inducible factor-2α(hif-2alpha) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2(Flk-1)［J］. J Biol Chem, 2003, 278(9): 7520-7530.
［2］Kasaharab Y, Tuder RM, Cool CD, Lynch DA, Flores SC, Voelkel NF. Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema［J］. Am J Respir Crit Care Med, 2001, 163(3 Pt 1): 737-744.
［3］McQuillan BM, Picard MH, Leavitt M, Weyman AE. Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects［J］.Circulation, 2001, 104(23): 2797-2802.
［4］McGoon MD. The assessment of pulmonary hypertension［J］. Clin Chest Med, 2001, 22(3): 493-508.
［6］Das R, Balonan L, Ballard HJ, Ho S. Chronic hypoxia inhibits the antihypertensive effect of melatonin on pulmonary artery［J］. Int J Cardiol, 2008, 126(3): 340-345.
［7］Schultz K, Fanburg BL, Beasley D. Hypoxia and hypoxia-inducible factor-1alpha promote growth factor-induced proliferation of human vascular smooth muscle cells［J］. Am J Physiol Heart Circ Physiol, 2006, 290(6): H2528-H2534.
［10］Endo A, Ayusawa M, Minato M, Takada M，Takahashi S, Harada K. Endogenous nitric oxide and endothelin-1 in persistent pulmonary hypertension of the newborn［J］. Eur J Pediatr, 2001, 160(4): 217-222.
［11］Wang J, Shimoda LA, Weigand L, Wang W, Sun D, Sylvester JT. Acute hypoxia increases intracellular ［Ca2+］in pulmonary arterial smooth muscle by enhancing capacitive Ca2+ entry［J］. Am J Physiol Lung Cell Mol Physiol, 2005, 288(6): L1059-L1069.
［12］McLaughlin VV, Sitbon O, Badesch DB, Barst RJ, Black C, Galiè N, et al. Survival with first-line bosentan in patients with primary pulmonary hypertension［J］. Eur Respir J, 2005, 25(2): 244-249.
［13］Hu R, Dai A, Tan S. Hypoxia-inducible factor 1 alpha upregulates the expression of inducible nitric oxide synthase gene in pulmonary arteries of hyposic rat［J］. Chin Med J (Engl), 2002, 115(12): 1833-1837.
［14］Kanazawa F,Nakanishi K,Osada H, Kanamaru Y, Ohrui N, Uenoyama M, et al. Expression of endothelin-1 in the brain and lung of rats exposed to permanent hypobarichypoxia［J］. Brain Res, 2005, 1036(1-2): 145-154.
