Endoglin regulates nitric oxide-dependent vasodilatation

23 p.-8 fig.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.This study was supported by grants from Comisión Interministerial de Ciencia y Tecnología(SAF2001/1701 to J. M. López-Novoa and SAF2000-0132 to C. Bernabéu); Comunidad Autónoma de Madrid (to C. Bernabéu); and Fondo de Investigación Sanitaria (PI020200 to C.Bernabéu). Dr. M. Jerkic is supported by a Visiting Professor Tenure of the Spanish Ministerio de Ciencia y Tecnología.Peer reviewe