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

Abstract

Activation of type 1 angiotensin (AT(1)) receptors causes hypertension, leading to progressive kidney injury. AT(1) 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(1) receptors on immune cells in the pathogenesis of hypertension by generating bone marrow chimeras with wild-type donors or donors lacking AT(1A) receptors (BMKO). The 2 groups had virtually identical blood pressures at baseline, suggesting that AT(1) 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(1) 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-1beta and interleukin-6. Thus, in angiotensin II-induced hypertension, bone marrow-derived AT(1) receptors limited mononuclear cell accumulation in the kidney and mitigated the chronic hypertensive response, possibly through the regulation of vasoactive cytokines.

• Authors: 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
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 55 Issue 1 Pg. 99-108 (Jan 2010) ISSN: 1524-4563 [Electronic] United States
• PMID: 19996062 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Agtr1a protein, mouse
• Ccl2 protein, mouse
• Chemokine CCL2
• Receptor, Angiotensin, Type 1
• Angiotensin II

Topics

• Albuminuria (chemically induced, genetics, urine)
• Angiotensin II
• Animals
• Blood Pressure (genetics, physiology)
• Bone Marrow Cells (metabolism)
• Bone Marrow Transplantation
• Cell Movement (genetics, physiology)
• Chemokine CCL2 (genetics)
• Female
• Gene Expression
• Hypertension (chemically induced, genetics, physiopathology)
• Kidney (metabolism, pathology)
• Lymphocytes (metabolism, pathology)
• Macrophages (metabolism, pathology)
• Male
• Mice
• Mice, Inbred Strains
• Mice, Knockout
• Receptor, Angiotensin, Type 1 (genetics, physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Transplantation Chimera (blood)