Endoglin regulates nitric oxide-dependent vasodilatation.
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.
Jerkic
Mirjana
M
Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología & Farmacología, Universidad de Salamanca, Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Rivas-Elena
Juan V
JV
Prieto
Marta
M
Carrón
Rosalia
R
Sanz-Rodríguez
Francisco
F
Pérez-Barriocanal
Fernando
F
Rodríguez-Barbero
Alicia
A
Bernabéu
Carmelo
C
López-Novoa
J M
JM
D000109:Acetylcholine / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D015703:Antigens, CD; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000633:toxicity; D002460:Cell Line; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D004790:Enzyme Induction / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000172:deficiency; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D020030:Nitric Oxide Donors; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester