Figure 5.

Vhl deletion in the renin cell lineage activates EPO expression in the kidney at a site that is typical for renin expression. (A) Hematocrit values of Vhl ^fl/fl and Vhl ^−/−REN mice show that Vhl ^−/−REN mice are markedly polycythemic: on normal salt diet, 66% were polycythemic, and on low-salt diet combined with the ACE inhibitor enalapril (LS+Enal) for 3 weeks, 69% were polycythemic versus Vhl ^fl/fl mice (49% and 47%, respectively). (B) Kidney EPO mRNA levels were increased in Vhl ^−/−REN mice: approximately 7-fold under baseline conditions and approximately 46-fold after RAS stimulation (LS+Enal) versus Vhl ^fl/fl mice. (C–F) In situ hybridization in kidney cortex of (D and F) Vhl ^−/−REN mice (LS+Enal for 3 weeks) localized EPO mRNA expression to afferent arterioles, which was more pronounced to their juxtaglomerular portions. Afferent arterioles in kidney sections of (C and E) Vhl ^fl/fl mice (LS+Enal for 3 weeks) were negative for EPO signal. Data are means ± SEM of 10 mice in each group. *P<0.005 by t test. Scale bar, 100 µm. Asterisks indicate glomeruli, and arrowheads show EPO-producing cells.