title: The upregulation of endothelial nitric oxide synthase and urotensin-II is associated with pulmonary hypertension and vascular diseases in rats produced by aortocaval shunting.
abstract: 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 +/- 0.35 kPa vs 2.09 +/- 0.38 kPa, 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.
authors.affiliation: Department of Pediatrics, First Hospital of Peking University, Xi An Men Street No. 1, 100034, Beijing, P.R. China.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Qi
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.forename: Xiuying
authors.initials: X
authors.lastname: Tang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Wei
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
mesh_terms: D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D002248:Carbon Monoxide / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D011651:Pulmonary Artery / Q000648:ultrastructure; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014579:Urotensins / Q000378:metabolism*; D014652:Vascular Diseases / Q000209:etiology* / Q000378:metabolism
chemical_list: D014579:Urotensins; D009569:Nitric Oxide; D002248:Carbon Monoxide; C029677:urotensin II; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1