Increased AT₁ receptor expression and mRNA in kidney glomeruli of AT₂ receptor gene-disrupted mice

The proposed feedback between angiotensin II AT₂ and AT₁ receptors prompted us to study AT₁ receptor expression in kidneys of male AT₂ receptor-gene disrupted mice (agtr2 -/y). In wild-type (agtr2 +/y) mice, AT₁ receptor binding and mRNA is abundant in glomeruli, and AT₁ receptor binding is also high in the inner stripe of the outer medulla. AT₂ receptors are scarce, primarily associated to cortical vascular structures. In agtr2 -/y mice, AT₁ receptor binding and mRNA were increased in the kidney glomeruli, and AT₁ receptor binding was higher in the rest of the cortex and outer stripe of the outer medulla, but not in its inner stripe, indicating different cellular regulation. Although AT₂ receptor expression is very low in male agtr 2 +/y mice, their gene disruption alters AT₁ receptor expression. AT₁ upregulation alone may explain the AT₂ gene-disrupted mice phenotype such as increased blood pressure, higher sensitivity to angiotensin II, and altered renal function. The indirect AT₁/AT₂ receptor feedback could have clinical significance because AT₁ antagonists are widely used in medical practice.