Jerkic Mirjana, Rivas-Elena Juan V, Prieto Marta, Carrón Rosalia, Sanz-Rodríguez Francisco, Pérez-Barriocanal Fernando, Rodríguez-Barbero Alicia, Bernabéu Carmelo, López-Novoa J M
Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología & Farmacología, Universidad de Salamanca, Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
FASEB J. 2004 Mar;18(3):609-11. doi: 10.1096/fj.03-0197fje. Epub 2004 Jan 20.
Endoglin is a membrane glycoprotein that plays an important role in cardiovascular development and angiogenesis. We examined the role of endoglin in the control of vascular tone by measuring nitric oxide (NO)-dependent vasodilation in haploinsufficient mice (Eng+/-) and their Eng+/+ littermates. The vasodilatory effect of acetylcholine, bradykinin, and sodium nitroprusside was assessed in anesthetized mice; in isolated, perfused hindlimbs; and in aortic rings. The substantial hypotensive and vasodilatory response induced by acetylcholine and bradykinin in Eng+/+ was markedly reduced in Eng+/- mice. Both kinds of animals had similar responses to sodium nitroprusside, suggesting that the deficient vasodilatory effect is not due to a NO response impairment. Urinary and plasma concentrations of nitrites, a NO metabolite, were lower in Eng+/- than in Eng+/+ mice. The levels of endothelial nitric oxide synthase (eNOS) in kidneys and femoral arteries were about half in Eng+/- than in Eng+/+ mice and were also reduced in primary cultures of aortic endothelial cells from Eng+/- compared with those from Eng+/+ mice. Furthermore, overexpression or suppression of endoglin in cultured cells induced a marked increase or decrease in the protein levels of eNOS, respectively. Thus, our results in vivo and in vitro demonstrate a relationship between endoglin and NO-dependent vasodilation mediated by the regulation of eNOS expression.
内皮糖蛋白是一种膜糖蛋白，在心血管发育和血管生成中起重要作用。我们通过测量单倍体不足小鼠（Eng+/-）及其Eng+/+同窝小鼠中一氧化氮（NO）依赖性血管舒张，研究了内皮糖蛋白在血管张力控制中的作用。在麻醉小鼠、离体灌注后肢和主动脉环中评估了乙酰胆碱、缓激肽和硝普钠的血管舒张作用。Eng+/+小鼠中由乙酰胆碱和缓激肽诱导的显著降压和血管舒张反应在Eng+/-小鼠中明显降低。两种动物对硝普钠的反应相似，表明血管舒张作用不足并非由于NO反应受损。Eng+/-小鼠尿液和血浆中NO代谢产物亚硝酸盐的浓度低于Eng+/+小鼠。Eng+/-小鼠肾脏和股动脉中内皮型一氧化氮合酶（eNOS）的水平约为Eng+/+小鼠的一半，与Eng+/+小鼠相比，Eng+/-小鼠主动脉内皮细胞原代培养物中的eNOS水平也降低。此外，在培养细胞中过表达或抑制内皮糖蛋白分别导致eNOS蛋白水平显著升高或降低。因此，我们体内和体外的结果证明了内皮糖蛋白与通过调节eNOS表达介导的NO依赖性血管舒张之间的关系。
