Increased Angiotensin II AT1 receptor mRNA and binding in spleen and lung of AT2 receptor gene disrupted mice

To clarify the relationship between Angiotensin II AT1 and AT2 receptors, we studied AT1 receptor mRNA and binding expression in tissues from AT2 receptor gene disrupted (AT2−/−) female mice, where AT2 receptors are not expressed in vivo, using in situ hybridization and quantitative autoradiography. Wild type mice expressed AT1A receptor mRNA and AT1 receptor binding in lung parenchyma, the spleen, predominantly in the red pulp, and in liver parenchyma. In wild type mice, lung AT2 receptors were expressed in lung bronchial epithelium and smooth muscle, and were not present in the lung parenchyma, the spleen or the liver. This indicates that AT1 and AT2 receptors were not expressed in the same cells. In AT2−/− mice, we found higher AT1A receptor mRNA and AT1 receptor binding in lung parenchyma and in the red pulp of the spleen, but not in the liver, when compared to littermate wild type controls. Our results suggest that impaired AT2 receptor function upregulates AT1 receptor transcription and expression in a tissue-specific manner and in cells not expressing AT2 receptors. AT1 upregulation explains the increased sensitivity to Angiotensin II characteristic of the AT2−/− phenotype, consistent with enhanced AT1 receptor activation in a number of tissues.