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Review
. 2011 Mar;57(3):355-62.
doi: 10.1161/HYPERTENSIONAHA.110.163519. Epub 2011 Jan 31.

Intratubular renin-angiotensin system in hypertension

L Gabriel Navar  1 , Hiroyuki Kobori, Minolfa C Prieto, Romer A Gonzalez-Villalobos
Affiliations
Review

Intratubular renin-angiotensin system in hypertension

L Gabriel Navar et al. Hypertension. 2011 Mar.
No abstract available

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Figures

Figure 1
Figure 1. A–C, Representative immunohistochemical analysis of rat kidney AGT from Sham, Ang II infused and Ang II infused plus AT1 receptor blockade groups
The immunoreactive areas were restricted only to proximal tubular cells. Vascular structures were negative. D, Kidney AGT immunostaining showed a significant enhancement in Ang II group (B) compared with sham group (A). ARB treatment prevented this augmentation (C). E, Representative Western blot analysis of urinary AGT levels among groups showing the stimulation in Ang II-infused group. F, Urinary excretion rates of AGT were enhanced 4.7-fold in Ang II-infused animals. ARB treatment prevented this augmentation. Ang II indicates angiotensin II; ARB, angiotensin II type1 receptor blocker, olmesartan; AGT, angiotensinogen. * P < 0.05 compared with the sham group. Data from Kobori et al. Hypertension 43:1126–1132, 2004.
Figure 2
Figure 2
Uriinary AGT (uAGT), expressed as ratio of uAGT/uCreatine, in normotensive, and in hypertensive patients (HTN) treated with renin-angiotensin system blockers (RASB) and compared with those treated with other drugs. *P<0.05 vs normotensive; P<0.05 vs HTN–RASB. Data from Kobori et al. Hypertension 53[Part 2]:344–350, 2009.
Figure 3
Figure 3. Cascade of Intratubular RAS in Ang II Dependent Hypertension
In Ang II dependent hypertension, the kidney maintains de novo intrarenal Ang II formation enhanced proximal tubule AGT formation and spillover into distal nephron segments coupled with enhancement of CD renin and stimulation of tubular ACE. (Refer to text for relevant references).
Figure 4
Figure 4. Renin immunoreactivity in juxtaglomerular (JG) cells and cortical collecting duct cells
Renin immunoreactivity by immunoperoxidase technique (A,C, and E) in paraffin embedded kidney sections (3 µm) from sham rats (A), and clipped (C) and non-clipped kidney (E) of Goldblatt rats. Specific JG renin immunoreactivity (arrows; DAB chromogen) in a sham (A) and in the clipped kidney (C) of a Goldblatt rat. Higher renin immunoreactivity (asterisks) are shown in the collecting ducts of the renal cortexes of both, clipped (C) and non-clipped (E) kidneys relative to the sham kidney (A). Densitometry the renin immunoreactivity in JG cells (B) and cortical (D) and medullary (F) collecting duct cells of sham, and clipped (CK) and non-clipped (NCK) kidneys of Goldblatt rats were performed using four kidney sections/animal (10 microscopic fields/kidney sections at the renal cortex and medulla regions) and compared to sham kidneys. Sham rats (n= 5). Goldblatt rats (n= 6). Glom: Glomerulus. Values are mean ± S.E. *P<0.0001 versus sham. Renin antibody dilution 1:4,000. *P<0.05 versus sham. #P< 0.05 clipped kidney versus non-clipped. CD: collecting duct; JG: juxtaglomerular; CK: clipped kidney; NCK: non-clipped kidney; IDV: integrated densitometric values. Modified from Prieto-Carrasquero et al. Hypertension 51:1590–1596, 2008.
Figure 5
Figure 5. Double immunolabeling for renin and (pro)renin receptor ((P)RR) in the chronic Ang II-infused rat kidney
Double immunolabeling for renin (red) and (P)RR (green) was performed to confirm that renin is localized in principal cells (asterisks) while (P)RR is expressed in intercalated cells (arrows). A rabbit polyclonal anti-renin antibody (T. Inagami, Vanderbilt University) at a 1:4,000 dilution detected by a fluorescent secondary antibody (Alexa Fluor 594, red; Invitrogen) chicken anti-rabbit, was followed by a goat anti-(P)RR antibody (Abcam 5959, Cambridge, MA) at 1:400 dilution detected with a fluorescent secondary antibody donkey anti-goat (Alexa Fluor 488, green; Invitrogen). (Unpublished data)
Figure 6
Figure 6. Changes in mean arterial blood pressure and intrarenal Ang II in Ang II-infused mice with or without an ACE inhibitor
Blood pressure and Ang II concentrations were determined by telemetry and radioimmunoanalysis respectively. Ang II = Angiotensin II (400 ng/kg/min), ACEi = Lisinopril (100 mg/L in the drinking water). *p < 0.05 vs. controls by TWO-WAY ANOVA for MAP changes and ONE-WAY ANOVA for Ang II changes. (From Gonzalez-Villalobos et al. Hypertension 53:351–355, 2009).
See this image and copyright information in PMC

References

    1. Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 2007;59:251–287. - PubMed
    1. Navar LG, Harrison-Bernard LM, Nishiyama A, Kobori H. Regulation of intrarenal angiotensin II in hypertension. Hypertension. 2002;39:316–322. - PMC - PubMed
    1. Navar LG, Prieto-Carrasquero MC, Kobori H. Molecular aspects of the renal renin-angiotensin system. In: Re R, DiPette DJ, Schiffrin EL, Sowers JR, editors. Molecular Mechanisms in Hypertension. Taylor & Francis Group; 2006. pp. 3–14.
    1. Douglas JG, Hopfer U. Novel aspects of angiotensin receptors and signal transduction in the kidney. Annu Rev Physiol. 1994;56:649–669. - PubMed
    1. Navar LG, Harrison-Bernard LM, Imig JD, Mitchell KD. Renal actions of angiotensin II at AT1 receptor blockers. In: Epstein M, Brunner HR, editors. Angiotensin II Receptor Antagonists. Philadelphia: Hanley & Belfus, Inc.; 2000. pp. 189–214.

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