The upregulation of endothelial nitric oxide synthase and urotensin-II is associated with pulmonary hypertension and vascular diseases in rats produced by aortocaval shunting

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• 作者：Jianguang Qi ; Junbao Du ; Xiuying Tang ; Jian Li ; Bing Wei and Chaoshu Tang
• 关键词：Nitric oxide ; Carbon monoxide ; Urotensin ; II ; Pulmonary hypertension ; Left to right shunt
• 刊名：Heart and Vessels
• 出版年：2004
• 出版时间：March 2004
• 年：2004
• 卷：19
• 期：2
• 页码：81-88
• 全文大小：503 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Cardiology
  Cardiac Surgery
  Vascular Surgery
  Biomedical Engineering
  Interventional Radiology
  Ultrasound
  
• 出版者：Springer Japan
• ISSN：1615-2573

文摘

The mechanism of pulmonary vascular structural remodeling and pulmonary hypertension induced by high pulmonary blood flow is still unclear. Nitric oxide (NO) and carbon monoxide (CO) are two gaseous molecules recently discovered; both can induce the relaxation of blood vessels and inhibit the proliferation of vascular smooth muscle cells. More recently, urotensin-II (U-II) has been considered as the most potent mammalian vasoconstrictor identified so far, which can promote the proliferation of vascular smooth muscle cells. The aim of this study was to investigate the alteration of micro- and ultrapathologic structure, gaseous molecules, and U-II in rats with pulmonary hypertension induced by increased pulmonary blood flow. Aortocaval shunting was produced in rats. After 11-weeks of shunting, pulmonary artery mean pressure (PAMP) was measured. Pulmonary vascular micro- and ultrastructure was examined. Meanwhile, the concentration of plasma NO and CO was measured by spectrophotometry. The expression of endothelial nitric oxide synthase (eNOS), heme oxygenase-1 (HO-1), and U-II by pulmonary arteries was detected by immunohistochemistry. The results showed that PAMP was significantly elevated after 11 weeks of aortocaval shunting (2.99 ± 0.35kPa vs 2.09 ± 0.38kPa, P 0.01). Muscularization of small pulmonary vessels and relative medial thickness of pulmonary arteries were obviously increased in shunt rats compared with controls. Ultrastructural changes were found in intrapulmonary arteries of shunt rats. Meanwhile, plasma NO concentration was increased and eNOS expression by pulmonary artery endothelial cells was significantly augmented in rats of the shunting group, but there was no significant difference in plasma CO level and HO-1 expression by pulmonary artery smooth muscle cells between shunting and sham groups. Urotensin-II expression by pulmonary artery endothelial cells and smooth muscle cells was significantly strengthened in shunt rats compared with sham rats. The results suggest that pulmonary vascular structural remodeling is an important pathologic basis of pulmonary hypertension induced by a left-to-right shunt. Upregulation of U-II might play an important role in the development of high pulmonary blood flow-induced pulmonary hypertension. Nitric oxide, as a modifying factor, might be involved in the regulation of pulmonary vascular structural remodeling.