Increased AT 1 receptor expression and mRNA in kidney glomeruli of AT 2 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 AT1antagonists are widely used in medical practice.Fil: Saavedra, Juan M.. National Institute of Mental Health; Estados UnidosFil: Häuser, Walter. National Institute of Mental Health; Estados UnidosFil: Ciuffo, Gladys Maria. National Institute of Mental Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Egidy, Giorgia. National Institute of Mental Health; Estados UnidosFil: Hoe, Kwang Lae. National Institute of Mental Health; Estados UnidosFil: Jöhren, Olaf. National Institute of Mental Health; Estados UnidosFil: Sembonmatsu, Takaaki. Vanderbilt University; Estados UnidosFil: Inagami, Tadashi. Vanderbilt University; Estados UnidosFil: Armando, Inés. National Institute of Mental Health; Estados Unido

Increased AT\u3csub\u3e1\u3c/sub\u3e receptor expression and mRNA in kidney glomeruli of AT\u3csub\u3e2\u3c/sub\u3e 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