A Role for Angiotensin II Type 1 Receptors on Bone Marrow-Derived Cells in the Pathogenesis of AngiotensinII–Dependent Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 55; no. 1; pp. 99 - 108
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: 07-12-2009
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.109.144964

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-1
β
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.