Oxygen Radicals and Substance P in Perinatal Hypoxia-Exaggerated, Monocrotaline-Induced Pulmonary Hypertension

Kang-Hua Chen ； Yih-Loong Lai ； Mei-Jung Chen

《The Chinese Journal of Physiology》 55卷2期 (2012/04) Pp. 82-90

https://doi.org/10.4077/CJP.2012.AMM103

並列摘要

Perinatal hypoxia has been observed to cause more aggressive pulmonary hypertension in human. Several mediators such as reactive oxygen species (ROS) and substance P are believed to be crucial in the mechanism of inducing pulmonary hypertension. This study was designed to test whether substance P and ROS play a role in perinatal hypoxia-exaggerated, monocrotaline (MCT)-induced pulmonary hypertension. Normoxic Wistar rats (weighing 258 ±9 g, n = 31) were divided into two groups: control (n = 16) and MCT (n = 15). Perinatal hypoxia Wistar rats (weighing 260 ±19 g, n = 49) were divided into six groups: Hypoxia (n = 8), Hypoxia+MCT (n = 8), Hypoxia+capsaicin (CP)+MCT (n = 7), Hypoxia+MCT+1,3-dimethyl-2- thiourea (DMTU)E (n = 10), Hypoxia+MCT+DMTU(subscript L) (n = 9), and Hypoxia+MCT+ hexa(sulfobutyl) fullerenes (HSF) (n = 7). Rats in the control group received saline injections. MCT (60 mg/kg, s.c.) was given three weeks prior to the functional examination. Chronic capsaicin pretreatment was performed to deplete substance P. Hydroxyl radical scavenger DMTU (500 mg/kg) was intraperitoneally (i.p.) injected early (DMTU(subscript E)) or late (DMTU(subscript L)) after MCT. Antioxidant HSF (10 mg/kg, i.p.) was given once daily for three weeks following MCT. MCT treatment caused significant increases in pulmonary arterial pressure (Ppa) and substance P level in lung tissue in normoxic rats. The MCT-induced increase in pulmonary arterial blood pressure was exaggerated by perinatal hypoxia, but this exaggeration was attenuated by either capsaicin pretreatment or antioxidant administrations. These results suggest that both ROS and substance P are involved in perinatal hypoxia-augmented, MCT-induced pulmonary hypertension.

並列關鍵字

substance P ； reactive oxygen species ； perinatal hypoxia ； pulmonary hypertension ； antioxidants

參考文獻

Chen, K. H.,Chen, Y. J.,Yang, C. H.,Liu, K. W.,Chang, J. L.,Pan, S. F.,Lin, T. B.,Chen, M. J.(2012).Attenuation of the extract from Moringa oleifera on monocrotaline-induced pulmonary hypertension in rats.Chinese J. Physiol..55(1),22-30.

Guo, H.,Hu, L. M.,Wang, S. X.,Wang, Y. L.,Shi, F.,Li, H.,Liu, Y.,Kang, L. Y.,Gao, X. M.(2011).Neuroprotective effects of scutellarin against hypoxic-ischemic-induced cerebral injury via augmentation of antioxidant defense capacity.Chinese J. Physiol..54(6),399-405.

Liu, Y.,Zhang, B.,Dong, M. Q.,Niu, W.,Luo, Y.,Gao, Y. Q.,Li, Z. C.(2010).Attenuation of pulmonary arterial smooth muscle cell proliferation following hypoxic pulmonary hypertensia by the Na+/H+ exchange inhibitor amiloride.Chinese J. Physiol..53(1),36-44.

Aziz, S. M.,Toborek, M.,Hennig, B.,Mattson, M. P.,Guo, H.,Lipke, D. W.(1997).Oxidative stress mediates monocrotaline-induced alterations in tenascin expression in pulmonary artery endothelial cells.Int. J. Biochem. Cell Biol..29(5),775-787.

Barker, D. J.(1990).The fetal and infant origins of adult disease.Brit. Med. J..301(6761),1111.