Altered pulmonary vascular reactivity in mice with excessive erythrocytosis

被引:33
作者
Hasegawa, J
Wagner, KF
Karp, D
Li, DC
Shibata, J
Heringlake, M
Bahlmann, L
Depping, R
Fandrey, J
Schmucker, P
Uhlig, S
机构
[1] Res Ctr Borstel, Ctr Med & Biosci, Div Pulm Pharmacol, D-23845 Borstel, Germany
[2] Univ Essen Gesamthsch, Dept Physiol, D-4300 Essen 1, Germany
[3] Med Univ Lubeck, Dept Anesthesiol & Crit Care Med, D-23538 Lubeck, Germany
[4] Med Univ Lubeck, Dept Physiol, D-23538 Lubeck, Germany
关键词
pulmonary hypertension; erythropoietin; isolated mouse lung; vascular remodeling;
D O I
10.1164/rccm.200308-1154OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Pulmonary vascular remodeling during chronic hypoxia may be the result of either oxygen deprivation or erythrocytosis. To separate experimentally the effects of hypoxia and erythrocytosis, we analyzed transgenic mice that constitutively overexpress the human erythropoietin gene in an oxygen-independent manner. These mice are characterized by polycythemia but have normal blood pressure, heart rate, and cardiac output. In transgenic mice, pulmonary artery pressure (PAP) was increased in vivo but was reduced in blood-free perfused lungs. The thromboxane receptor agonist U46619 caused a smaller rise in PAP in isolated transgenic lungs than in lungs from wild-type mice. The transgenic pulmonary vasculature was characterized by elevated prostacyclin production, stronger endothelial nitric oxide synthase expression, and reduced pulmonary vascular smooth muscle thickness. The fact that transgenic polycythemic mice have marked pulmonary hypertension in vivo but not in vitro suggests that their pulmonary hypertension is due to the increased blood viscosity, thus supporting an independent role of polycythemia in the development of pulmonary hypertension. In addition, our findings indicate that the lungs of transgenic animals adapt to the high PAP by elevated synthesis of vasodilators and reduced vascular smooth muscle thickness that tend to reduce vascular tone and vascular responsiveness.
引用
收藏
页码:829 / 835
页数:7
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