Type 1 Angiotensin Receptors on CD11c-Expressing Cells Protect Against Hypertension by Regulating Dendritic...

Area of Science:

• Immunology
• Cardiovascular Research
• Renal Physiology

Background:

• Type 1 angiotensin (AT1) receptors are present on immune cells.
• Previous studies indicated bone marrow-derived AT1 receptors protect against angiotensin II-induced hypertension.
• CD11c+ myeloid cells, including dendritic cells (DCs), activate T lymphocytes.

Purpose of the Study:

• To investigate the role of AT1 receptors on CD11c+ cells in the pathogenesis of hypertension.
• To determine if AT1 receptors on dendritic cells influence the hypertensive response to angiotensin II.

Main Methods:

• Created mice lacking the AT1a receptor isoform on CD11c+ cells (DC AT1aR KO).
• Subjected DC AT1aR KO and wild-type (WT) mice to chronic angiotensin II infusion.
• Measured blood pressure using radiotelemetry and assessed renal immune cell infiltration and sodium excretion.

Main Results:

• DC AT1aR KO mice exhibited exaggerated hypertensive responses to angiotensin II.
• Enhanced accumulation of effector memory T cells and CD40+ DCs was observed in the kidneys of KO mice.
• KO mice showed increased CCL5 and CCR7 expression on DCs, elevated renal sodium channel subunit expression, and reduced sodium excretion.

Conclusions:

• AT1a receptor stimulation on dendritic cells suppresses DC maturation and T cell activation.
• This suppression confers protection against sodium retention and elevated blood pressure.
• Targeting AT1a receptors on dendritic cells may offer a therapeutic strategy for hypertension.