Abstract
Chronic angiotensin II (AngII) infusion leads to hypertension and stimulation of proximal tubule angiotensinogen and augmentation of collecting duct (CD) renin, specifically in principal cells. The present study was performed to determine if the enhancement of CD renin in AngII-dependent hypertension is a direct effect of AngII or primarily due to the elevated arterial blood pressure by evaluating renin mRNA and protein levels separately in renal cortex and medulla of both kidneys in two-kidney, one-clip rats (2K1C) prepared by placing a 0.25mm clip on left renal artery. After 25days, systolic blood pressure in 2K1C (n=8) was 196 ± 3mm Hg compared to 116 ± 2mm Hg in sham-operated rats (n=8); kidney (0.2 ± 0.0 vs. 1.0 ± 0.0 DU) but increased in the clipped kidney (1.7 ± 1.0 vs. 1.0 ± 0.0 DU) compared to sham. However, renin immunoreactivity in cortical and medullary CDs increased in both kidneys of 2K1C rats compared to sham (clipped=2.8 ± 1.5 cortex; 2.1 ± 1.0 medulla; non-clipped=4.6 ± 2.3 cortex; 3.2 ± 0.8 medulla vs. 1.0 ± 0.0 DU) compared to sham. Renin protein levels assessed by Western blot in kidney medulla of 2K1C rats were also increased compared to sham (1.4 ± 0.2 in clipped and 1.5 ± 0.3 in non-clipped). Likewise, renin mRNA levels measured by real-time qRT-PCR were higher in medullary tissue from both kidneys of 2K1C (clipped=10 ± 4.0; non-clipped=4.3 ± 2.6) compared to sham rats. Increased expression of renin in principal cells of CDs of clipped as well as non- clipped kidneys is consistent with the hypothesis that intrarenal AngII levels stimulate renin in distal nephron segment independently of high blood pressure. The increased distal tubular renin may contribute to increased intrarenal and intratubular AngII formation in AngII-dependent hypertension. Supported by grants from NIH (P20RR017659), HL 26371, AHA-0325269B and the Louisiana Board of Regents Millennium Excellence Fund (2001-06-07).
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