Abstract
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.
MeSH terms
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Acetylcholine / pharmacology
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Acetylcholine / toxicity
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Animals
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Antigens, CD
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Blood Pressure / drug effects
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Bradykinin / toxicity
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Cell Line
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Endoglin
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Endothelial Cells / metabolism
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Endothelium, Vascular / metabolism*
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Enzyme Induction / physiology
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Hypotension / chemically induced
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Kidney / metabolism
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Lung / metabolism
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Mice
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Mice, Knockout
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Myoblasts / cytology
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Myoblasts / metabolism
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NG-Nitroarginine Methyl Ester / pharmacology
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Nitric Oxide / physiology*
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Nitric Oxide Donors / pharmacology
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Nitric Oxide Synthase / biosynthesis*
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase Type II
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Nitric Oxide Synthase Type III
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Nitroprusside / pharmacology
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Receptors, Cell Surface
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / physiology
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Transfection
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Transforming Growth Factor beta / deficiency
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Transforming Growth Factor beta1
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Vascular Cell Adhesion Molecule-1 / biosynthesis
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / physiology*
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Vasoconstrictor Agents / pharmacology
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Vasodilation / physiology*
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Vasodilator Agents / pharmacology
Substances
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Antigens, CD
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ENG protein, human
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Endoglin
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Nitric Oxide Donors
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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TGFB1 protein, human
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Tgfb1 protein, mouse
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Vascular Cell Adhesion Molecule-1
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Vasoconstrictor Agents
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Vasodilator Agents
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Nitroprusside
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Nitric Oxide
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nitric Oxide Synthase Type III
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Nos3 protein, mouse
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Acetylcholine
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Bradykinin
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NG-Nitroarginine Methyl Ester