Increased AT(1) receptor expression and mRNA in kidney glomeruli of AT(2) receptor gene-disrupted mice

The proposed feedback between angiotensin II AT(2) and AT(1) receptors prom pted us to study AT(1) receptor expression in kidneys of male AT(2) recepto r-gene disrupted mice (agtr2 -/y). In wild-type (agtr2 +/y) mice, AT(1) rec eptor binding and mRNA is abundant in glomeruli, and AT(1) receptor binding is also high in the inner stripe of the outer medulla. AT(2) receptors are scarce, primarily associated to cortical vascular structures. In agtr2 -/y mice, AT(1) receptor binding and mRNA were increased in the kidney glomeru li, and AT(1) receptor binding was higher in the rest of the cortex and out er stripe of the outer medulla, but not in its inner stripe, indicating dif ferent cellular regulation. Although AT(2) receptor expression is very low in male agtr2 +/y mice, their gene disruption alters AT(1) receptor express ion. AT(1) upregulation alone may explain the AT(2) gene-disrupted mice phe notype such as increased blood pressure, higher sensitivity to angiotensin II, and altered renal function. The indirect AT(1)/AT(2) receptor feedback could have clinical significance because AT(1) antagonists are widely used in medical practice.