A Role for Angiotensin II Type 1 Receptors on Bone Marrow-Derived Cells in the Pathogenesis of Angiotensin II–Dependent Hypertension
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- Steven D. Crowley
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Young-Soo Song
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Gregory Sprung
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Robert Griffiths
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Matthew Sparks
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Ming Yan
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- James L. Burchette
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- David N. Howell
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Eugene E. Lin
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Benson Okeiyi
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Johannes Stegbauer
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Yanqiang Yang
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Pierre-Louis Tharaux
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
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- Phillip Ruiz
- From the Division of Nephrology, Departments of Medicine (S.D.C., Y.-S.S., G.S., R.G., M.S., M.Y., E.E.L., B.O., J.S., Y.Y.) and Pathology (J.L.B., D.N.H.), Duke University Medical Center and Durham Veterans’ Affairs Medical Center, Durham, N.C.; Paris Cardiovascular Research Center (P.-L.T.), Institut National de la Sante et de la Recherche Medicale, Université Paris Descarte, Paris, France; Department of Pathology (P.R.), University of Miami, Miami, Fla.
説明
<jats:p> Activation of type 1 angiotensin (AT <jats:sub>1</jats:sub> ) receptors causes hypertension, leading to progressive kidney injury. AT <jats:sub>1</jats:sub> receptors are expressed on immune cells, and previous studies have identified a role for immune cells in angiotensin II–dependent hypertension. We, therefore, examined the role of AT <jats:sub>1</jats:sub> receptors on immune cells in the pathogenesis of hypertension by generating bone marrow chimeras with wild-type donors or donors lacking AT <jats:sub>1A</jats:sub> receptors (BMKO). The 2 groups had virtually identical blood pressures at baseline, suggesting that AT <jats:sub>1</jats:sub> receptors on immune cells do not make a unique contribution to the determination of baseline blood pressure. By contrast, in response to chronic angiotensin II infusion, the BMKOs had an augmented hypertensive response, suggesting a protective effect of AT <jats:sub>1</jats:sub> receptors on immune cells with respect to blood pressure elevation. The BMKOs had 50% more albuminuria after 4 weeks of angiotensin II–dependent hypertension. Angiotensin II–induced pathological injury to the kidney was similar in the experimental groups. However, there was exaggerated renal expression of the macrophage chemokine monocyte chemoattractant protein 1 in the BMKO group, leading to persistent accumulation of macrophages in the kidney. This enhanced mononuclear cell infiltration into the BMKO kidneys was associated with exaggerated renal expression of the vasoactive mediators interleukin-1β and interleukin-6. Thus, in angiotensin II–induced hypertension, bone marrow–derived AT <jats:sub>1</jats:sub> receptors limited mononuclear cell accumulation in the kidney and mitigated the chronic hypertensive response, possibly through the regulation of vasoactive cytokines. </jats:p>
収録刊行物
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- Hypertension
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Hypertension 55 (1), 99-108, 2010-01
Ovid Technologies (Wolters Kluwer Health)
