A role for angiotensin II type 1 receptors on bone marrow-derived cells in the pathogenesis of angiotensin II-dependent hypertension

Steven D. Crowley, Young Soo Song, Gregory Sprung, Robert Griffiths, Matthew Sparks, Ming Yan, James L. Burchette, David N. Howell, Eugene E. Lin, Benson Okeiyi, Johannes Stegbauer, Yanqiang Yang, Pierre Louis Tharaux, Phillip Ruiz

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Activation of type 1 angiotensin (AT1) receptors causes hypertension, leading to progressive kidney injury. AT1 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 AT1 receptors on immune cells in the pathogenesis of hypertension by generating bone marrow chimeras with wild-type donors or donors lacking AT1A receptors (BMKO). The 2 groups had virtually identical blood pressures at baseline, suggesting that AT1 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 AT1 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 AT1 receptors limited mononuclear cell accumulation in the kidney and mitigated the chronic hypertensive response, possibly through the regulation of vasoactive cytokines.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalHypertension
Volume55
Issue number1
DOIs
StatePublished - Jan 1 2010

Fingerprint

Angiotensin Type 1 Receptor
Angiotensin II
Bone Marrow Cells
Hypertension
Kidney
Bone Marrow
Blood Pressure Determination
Macrophages
Blood Pressure
Albuminuria
Chemokine CCL2
Wounds and Injuries
Interleukin-1
Chemokines
Interleukin-6
Cytokines

Keywords

  • Angiotensin II
  • Hypertension
  • Inflammation
  • Kidney diseases
  • Lymphocytes

ASJC Scopus subject areas

  • Internal Medicine

Cite this

A role for angiotensin II type 1 receptors on bone marrow-derived cells in the pathogenesis of angiotensin II-dependent hypertension. / Crowley, Steven D.; Song, Young Soo; Sprung, Gregory; Griffiths, Robert; Sparks, Matthew; Yan, Ming; Burchette, James L.; Howell, David N.; Lin, Eugene E.; Okeiyi, Benson; Stegbauer, Johannes; Yang, Yanqiang; Tharaux, Pierre Louis; Ruiz, Phillip.

In: Hypertension, Vol. 55, No. 1, 01.01.2010, p. 99-108.

Research output: Contribution to journalArticle

Crowley, SD, Song, YS, Sprung, G, Griffiths, R, Sparks, M, Yan, M, Burchette, JL, Howell, DN, Lin, EE, Okeiyi, B, Stegbauer, J, Yang, Y, Tharaux, PL & Ruiz, P 2010, 'A role for angiotensin II type 1 receptors on bone marrow-derived cells in the pathogenesis of angiotensin II-dependent hypertension', Hypertension, vol. 55, no. 1, pp. 99-108. https://doi.org/10.1161/HYPERTENSIONAHA.109.144964
Crowley, Steven D. ; Song, Young Soo ; Sprung, Gregory ; Griffiths, Robert ; Sparks, Matthew ; Yan, Ming ; Burchette, James L. ; Howell, David N. ; Lin, Eugene E. ; Okeiyi, Benson ; Stegbauer, Johannes ; Yang, Yanqiang ; Tharaux, Pierre Louis ; Ruiz, Phillip. / A role for angiotensin II type 1 receptors on bone marrow-derived cells in the pathogenesis of angiotensin II-dependent hypertension. In: Hypertension. 2010 ; Vol. 55, No. 1. pp. 99-108.
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