Increased Collecting Duct Renin Protein Expression in Cyp1a1‐Ren2 Transgenic Rats with Inducible Ang II‐dependent Malignant Hypertension.

Abstract

In angiotensin II (AngII)‐dependent hypertension, renin is upregulated in collecting ducts (CD) despite suppression of plasma renin activity and renin in juxtaglomerular (JG) cells. The transgenic rat model with insertion of the mouse Ren2 gene [Cyp1a1‐Ren2 strain] exhibits renin expression only in the liver, enhancement of PRA, high circulating and intrarenal Ang II levels, and an inducible form of AngII‐dependent malignant hypertension by dietary administration of the aryl hydrocarbon, indole‐3‐carbinol (I3C). Although increased intrarenal AngII content in Cyp1a1‐Ren2 rats can be partially due to internalization via AT1R, de novo intrarenal Ang II formation is suspected in this model. This study determined the renin protein expression in the distal nephron segments as a potential pathway to explain the increased intrarenal AngII content in Cyp1a1‐Ren2 rats. Body weights decreased in hypertensive rats (248±0.2g) compared to controls (349±0.1g). Renin immunostaining was not suppressed in JG cells of Cyp1a1‐Ren2 rats (0.7±0.01 vs. 0.7±0.01DU). In contrast, CD renin immunoreactivity and renal medullary renin protein levels measured by Western blot were 3.8‐fold and 2.6‐fold higher in hypertensive rats than controls. Augmentation of CD renin may contribute to increase intrarenal Ang II content and, thereby, to the increased blood pressure in Cyp1a1‐Ren2 with AngII‐dependent malignant hypertension.