RESUMEN

The proposed feedback between angiotensin II AT(2) and AT(1) receptors prompted us to study AT(1) receptor expression in kidneys of male AT(2) receptor-gene disrupted mice (agtr2 -/y). In wild-type (agtr2 +/y) mice, AT(1) receptor 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 glomeruli, and AT(1) 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 AT(2) receptor expression is very low in male agtr 2 +/y mice, their gene disruption alters AT(1) receptor expression. AT(1) upregulation alone may explain the AT(2) gene-disrupted mice phenotype 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.

Asunto(s)

Glomérulos Renales/metabolismo , Receptores de Angiotensina/genética , Receptores de Angiotensina/metabolismo , Receptores de Angiotensina/fisiología , Angiotensina II/farmacología , Animales , Autorradiografía , Presión Sanguínea/efectos de los fármacos , Cruzamientos Genéticos , Retroalimentación , Genotipo , Imidazoles/farmacología , Corteza Renal/irrigación sanguínea , Corteza Renal/metabolismo , Médula Renal/metabolismo , Losartán/farmacología , Masculino , Ratones , Ratones Endogámicos , Ratones Noqueados , Especificidad de Órganos , Piridinas/farmacología , ARN Mensajero/genética , Receptor de Angiotensina Tipo 1 , Receptor de Angiotensina Tipo 2 , Receptores de Angiotensina/deficiencia , Transcripción Genética