Localization of angiotensin II type 1 receptor gene expression in rodent and human kidneys

The kidneys are an important target for angiotensin II (ANG II). In adult kidneys, the effects of ANG II are mediated mainly by ANG II type 1 (AT₁) receptors. AT₁ receptor expression has been reported for a variety of different cell types within the kidneys, suggesting a broad spectrum of actions for ANG II. Since there have been heterogeneous results in the literature regarding the intrarenal distribution of AT₁ receptors, this study aimed to obtain a comprehensive overview about the localization of AT₁ receptor expression in mouse, rat, and human kidneys. Using the cell-specific and high-resolution RNAscope technique, we performed colocalization experiments with various cell markers to specifically discriminate between different segments of the tubular and vascular system. Overall, we found a similar pattern of AT₁ mRNA expression in mouse, rat, and human kidneys. AT₁ receptors were detected in mesangial cells and renin-producing cells. In addition, AT₁ mRNA was found in interstitial cells of the cortex and outer medulla. In rodents, late afferent and early efferent arterioles expressed AT₁ receptor mRNA, but larger vessels of the investigated species showed no AT₁ expression. Tubular expression of AT₁ mRNA was species dependent with a strong expression in proximal tubules of mice, whereas expression was undetectable in human tubular cells. These findings suggest that the (juxta)glomerular area and tubulointerstitium are conserved expression sites for AT₁ receptors across species and might present the main target sites for ANG II in adult human and rodent kidneys.NEW & NOTEWORTHY Angiotensin II (ANG II) type 1 (AT₁) receptors are essential for mediating the effects of ANG II in the kidneys. This study aimed to obtain a comprehensive overview about the cell-specific localization of AT₁ receptor expression in rodent and human kidneys using the novel RNAscope technique. We found that the conserved AT₁ receptor mRNA expression sites across species are the (juxta)glomerular areas and tubulointerstitium, which might present main target sites for ANG II in adult human and rodent kidneys.