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 language||English (US)|
|Number of pages||10|
|State||Published - Jan 1 2010|
- Angiotensin II
- Kidney diseases
ASJC Scopus subject areas
- Internal Medicine