Prorenin receptor in distal nephron segments of 2-kidney, 1-clip goldblatt hypertensive rats.

ABSTRACT

BACKGROUND: The prorenin receptor (PRR) is expressed in the kidneys and has been localized to mesangial cells, renal arterioles, and distal nephron segments. By binding renin or prorenin, this receptor increases renin catalytic activity and activates prorenin. The renin gene is expressed by the principal cells of collecting ducts and is enhanced in angiotensin II (AngII)-dependent hypertension and in both kidneys of 2-kidney, 1-clip (2K1C) Goldblatt hypertensive rats. Colocalization of PRR with prorenin and renin in distal nephron segments may contribute to increased local AngII formation. METHODS: We examined the specific cell-type localization of PRR in distal nephron segments and the changes in PRR gene expression in both kidneys of 2K1C hypertensive rats (n=6) and sham-operated rats (n=5). RESULTS: After 25 days, systolic blood pressure and plasma renin activity increased to 186 ± 8 mmHg and 12.8 ± 3 ng/AngI/mL/hr, respectively, in 2K1C rats compared to controls (133 ± 9 mmHg and 7.1 ± 1 ng/AngI/mL/hr, respectively). Immunohistochemistry of the PRR on fixed kidney sections showed intense positive staining in the apical aspects of intercalated cells in collecting ducts. PRR immunoreactivity (clipped kidney 2.3 ± 1 IDU; nonclipped kidney 1.3 ± 0 IDU; sham 1.0 ± 0.0 IDU; P<0.05) and messenger RNA levels measured by quantitative real-time polymerase chain reaction (clipped kidney 1.3 ± 0.1 au; nonclipped kidney 0.9 ± 0.3 au; sham 1 ± 0.0 au; P<0.05] were increased in collecting duct cells of clipped kidneys of 2K1C rats compared to nonclipped and sham kidneys. CONCLUSION: The enhanced renin gene expression in the collecting ducts of hypertensive rats suggests that the renin secreted by principal cells is then anchored by the PRR on the intercalated cells, thus contributing to increased angiotensin peptide generation in distal nephron segments.