Abstract P314: Urinary Renin and Kidney RAS Activation in Mice with Diabetic Kidney Disease

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Johannes Rein ◽  
Patricia Valles ◽  
Jan Wysocki ◽  
Minghao Ye ◽  
Mariam Afkarian ◽  
...  
Keyword(s):  
Diabetic Kidney Disease ◽  
Plasma Renin ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Mesangial Expansion ◽  
Potential Source ◽  
Ras Activation ◽  
Collecting Tubule ◽  
Renin Mrna ◽  
Proximal Tubular

RAS is overactive in kidneys from patients with diabetic nephropathy (DN), but circulating plasma renin activity (PRA) is usually low. This is known as the renin-paradox. We evaluated juxtaglomerular (JGA), tubular and urinary renin, as a potential source of local RAS activation, to gain some understanding of this paradox. Mice with STZ induced diabetes were used which had mild albuminuria and glomerular mesangial expansion consistent with early DN. Renin expression in the JGA and in the collecting tubule (CT) was evaluated by immunohistochemistry. IF was used to localize renin within CT cells. Proximal tubular renin was evaluated by RT-real time PCR in microdissected proximal tubules (PT). Urinary renin and Ang II were measured by ELISA. Urinary Ang II was increased (37.8±11.4 vs. 99.0±21.6 pg/mg creat, p<0.05) reflecting an active kidney RAS. Urinary renin was also increased in STZ-treated as compared to controls (Table). In microdissected PTs there were no significant differences in renin mRNA between control and STZ-mice. By immunostaining, renin was localized to principal cells in the CT and the number of renin stained CTs was higher in STZ than in control mice. In sharp contrast, renin staining of the JGA of STZ-mice was significantly reduced as compared to controls. We conclude that in DN renin expression in the JGA, the physiologic site of renin secretion into the circulation is suppressed, whereas in the CT it is increased. Activation of the kidney RAS, as inferred from increased urinary Ang II, likely occurs as a result of renin of tubular origin rather than from JGA renin. Since PT renin is not increased, the CT may provide the source of tubular renin for RAS activation.

Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy

1993 ◽  
Vol 264 (5) ◽  
pp. F874-F881 ◽  
Author(s):  
S. S. el-Dahr ◽  
J. Gee ◽  
S. Dipp ◽  
B. G. Hanss ◽  
R. C. Vari ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Obstructive Nephropathy ◽  
Mrna Levels ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Kininase Ii ◽  
Plasma Angiotensin ◽  
Renin Mrna

The purpose of this study was to delineate the effects of prolonged (1 and 5 wk) unilateral ureteral obstruction (UUO) on the intrarenal renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood pressure (SBP) and plasma angiotensin (ANG) II levels were significantly higher at 1 and 5 wk of obstruction than in sham-operated groups. Also, plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05), and plasma angiotensin-converting enzyme (ACE)-kininase II activity was elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan (Dup 753) prevented the rise in SBP after UUO and normalized SBP in chronically hypertensive UUO rats. Renin mRNA levels and ANG II content were elevated in the obstructed kidneys at 1 and 5 wk compared with sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated in both the obstructed and contralateral kidneys at 5 wk compared with sham-operated kidneys (P < 0.05). In marked contrast to renin, total immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1 and 5 wk (P < 0.001). The results indicate that urinary obstruction activates renin and suppresses kallikrein gene expression. Activation of ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation and kinin degradation. The results implicate ANG II overproduction and kinin deficiency in the pathogenesis of UUO-induced hypertension and intrarenal vasoconstriction.

scholarly journals Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension

2014 ◽  
Vol 307 (8) ◽  
pp. F931-F938 ◽  
Author(s):  
Nirupama Ramkumar ◽  
Deborah Stuart ◽  
Sara Rees ◽  
Alfred Van Hoek ◽  
Curt D. Sigmund ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
Plasma Renin ◽  
Ang Ii ◽  
Water Excretion ◽  
Protein Levels ◽  
Renin Gene ◽  
Induced Hypertension ◽  
Renin Mrna ◽  
Exon 1

The physiological and pathophysiological significance of collecting duct (CD)-derived renin, particularly as it relates to blood pressure (BP) regulation, is unknown. To address this question, we generated CD-specific renin knockout (KO) mice and examined BP and renal salt and water excretion. Mice containing loxP-flanked exon 1 of the renin gene were crossed with mice transgenic for aquaporin-2-Cre recombinase to achieve CD-specific renin KO. Compared with controls, CD renin KO mice had 70% lower medullary renin mRNA and 90% lower renin mRNA in microdissected cortical CD. Urinary renin levels were significantly lower in KO mice (45% of control levels) while plasma renin concentration was significantly higher in KO mice (63% higher than controls) during normal-Na intake. While no observable differences were noted in BP between the two groups with varying Na intake, infusion of angiotensin II at 400 ng·kg−1·min−1 resulted in an attenuated hypertensive response in the KO mice (mean arterial pressure 111 ± 4 mmHg in KO vs. 128 ± 3 mmHg in controls). Urinary renin excretion and epithelial Na+ channel (ENaC) remained significantly lower in the KO mice following ANG II infusion compared with controls. Furthermore, membrane-associated ENaC protein levels were significantly lower in KO mice following ANG II infusion. These findings suggest that CD renin modulates BP in ANG II-infused hypertension and these effects are associated with changes in ENaC expression.

Control of renin secretion from kidneys with renin cell hyperplasia

2014 ◽  
Vol 306 (3) ◽  
pp. F327-F332 ◽  
Author(s):  
Birgül Kurt ◽  
Christian Karger ◽  
Charlotte Wagner ◽  
Armin Kurtz
Keyword(s):  
Plasma Renin ◽  
Renin Secretion ◽  
Ang Ii ◽  
Loss Of Function ◽  
Wild Type ◽  
Cell Hyperplasia ◽  
Absolute Level ◽  
Relative Level ◽  
Adult Kidney ◽  
Renin Mrna

In states of loss-of-function mutations of the renin-angiotensin-aldosterone system, kidneys develop a strong hyperplasia of renin-producing cells. Those additional renin cells are located outside the classic juxtaglomerular areas, mainly in the walls of preglomerular vessels and most prominently in multilayers surrounding afferent arterioles. Since the functional behavior of those ectopic renin cells is yet unknown, we aimed to characterize the control of renin secretion from kidneys with renin cell hyperplasia. As a model, we used kidneys from mice lacking aldosterone synthase (AS−/− mice), which displayed 10-fold elevations of renin mRNA and plasma renin concentrations. On the absolute level, renin secretion from isolated AS−/− kidneys was more than 10-fold increased over wild-type kidneys. On the relative level, the stimulation of renin secretion by the β-adrenergic activator isoproterenol or by lowering of the concentration of extracellular Ca2+ was very similar between the two genotypes. In addition, the inhibitory effects of ANG II and of perfusion pressure were similar between the two genotypes. Deletion of connexin40 blunted the pressure dependency of renin secretion and the stimulatory effect of low extracellular Ca2+ on renin secretion in the same manner in kidneys of AS−/− mice as in wild-type mice. Our findings suggest a high degree of functional similarity between renin cells originating during development and located at different positions in the adult kidney. They also suggest a high similarity in the expression of membrane proteins relevant for the control of renin secretion, such as β1-adrenergic receptors, ANG II type 1 receptors, and connexin40.

Defective nitric oxide production impairs angiotensin II-induced Na-K-ATPase regulation in spontaneously hypertensive rats

2012 ◽  
Vol 302 (1) ◽  
pp. F47-F51 ◽  
Author(s):  
Apurva A. Javkhedkar ◽  
Mustafa F. Lokhandwala ◽  
Anees Ahmed Banday
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
High Concentration ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Proximal Tubular ◽  
Stimulation Of

Angiotensin (ANG) II via ANG II type 1 receptors (AT1R) activates renal sodium transporters including Na-K-ATPase and regulates sodium homeostasis and blood pressure. It is reported that at a high concentration, ANG II either inhibits or fails to stimulate Na-K-ATPase. However, the mechanisms for these phenomena are not clear. Here, we identified the signaling molecules involved in regulation of renal proximal tubular Na-K-ATPase at high ANG II concentrations. Proximal tubules from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were incubated with low concentrations of ANG II (pM), which activated Na-K-ATPase in both the groups; however, the stimulation was more robust in SHR. A high concentration of ANG II (μM) failed to stimulate Na-K-ATPase in WKY rats. However, in SHR ANG II (μM) continued to stimulate Na-K-ATPase, which was sensitive to the AT1R antagonist candesartan. In the presence of NG-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthase (NOS) inhibitor, ANG II (μM) caused stimulation of Na-K-ATPase in proximal tubules of WKY rats while having no further stimulatory effect in SHR. ANG II (μM), via AT1R, increased proximal tubular NO levels in WKY rats but not in SHR. In SHR, NOS was uncoupled as incubation of proximal tubules with ANG II and l-arginine, a NOS substrate, caused superoxide generation only in SHR and not in WKY rats. The superoxide production in SHR was sensitive to l-NAME. There was exaggerated proximal tubular AT1R-G protein coupling and NAD(P)H oxidase activation in response to ANG II (μM) in proximal tubules of SHR compared with WKY rats. In SHR, inhibition of NADPH oxidase restored NOS coupling and ANG II-induced NO accumulation. In conclusion, at a high concentration ANG II (μM) activates renal NO signaling, which prevents stimulation of Na-K-ATPase in WKY rats. However, in SHR ANG II (μM) overstimulates NADPH oxidase, which impairs the NO system and leads to continued Na-K-ATPase activation.

Targeted deletion of NADPH-Oxidase Nox4 from proximal tubules is dispensable for diabetic kidney disease development

2020 ◽  
Author(s):  
Vicki Thallas-Bonke ◽  
Sih Min Tan ◽  
Runa S Lindblom ◽  
Matthew Snelson ◽  
Cesare Granata ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Nadph Oxidase ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Diabetic Kidney Disease ◽  
Proximal Tubules ◽  
Disease Development ◽  
Diabetic Kidney ◽  
Genetic Ablation ◽  
Proximal Tubular

Abstract Background The NADPH oxidase isoform, Nox4, mediates reactive oxygen species (ROS) production and renal fibrosis in diabetic kidney disease at the level of the podocyte. However, the mitochondrial localization of Nox4 and its role as a mitochondrial bioenergetic sensor has recently been reported. Whether Nox4 drives pathology in diabetic kidney disease within the proximal tubular compartment, which is densely packed with mitochondria, is not yet known. Methods We generated a proximal tubular specific Nox4 knockout mouse model by breeding Nox4flox/flox mice with mice expressing Cre recombinase under the control of the Sglt2 promoter. Subsets of Nox4ptKO mice and their Nox4flox/flox littermates were injected with streptozotocin (STZ) to induce diabetes. Mice were followed for 20 weeks and renal injury was assessed. Results Genetic ablation of proximal tubular Nox4 (Nox4ptKO) resulted in no change in renal function and histology. Nox4ptKO mice and Nox4flox/flox littermates injected with STZ exhibited the hallmarks of diabetic kidney disease including hyperfiltration, albuminuria, renal fibrosis and glomerulosclerosis. Surprisingly, diabetes-induced renal injury was not improved in Nox4ptKOSTZ mice compared to Nox4flox/flox STZ mice. Although diabetes conferred ROS overproduction and increased mitochondrial oxygen consumption rate, proximal tubular deletion of Nox4 did not normalize oxidative stress or mitochondrial bioenergetics. Conclusion Taken together, these results demonstrate that genetic deletion of Nox4 from the proximal tubules does not influence diabetic kidney disease development, indicating that Nox4 localization within this highly energetic compartment is dispensable for chronic kidney disease pathogenesis in the setting of diabetes.

Abstract 17: Genetic Deletion Of Angiotensin Ii AT 1a Receptors Selectively In The Proximal Tubules Of The Kidney Attenuates Two-kidney, One-clip Goldblatt Hypertension In Pt- Agtr1a -/- Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Xiao C Li ◽  
Ana Leite ◽  
Rumana Hassan ◽  
Akemi Sato ◽  
Courtney Dugas ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mrna Expression ◽  
Proximal Tubules ◽  
Maximal Response ◽  
Internal Diameter ◽  
Dependent Manner ◽  
Ang Ii ◽  
Renin Mrna ◽  
Genetic Deletion ◽  
Goldblatt Hypertension

The activation of the renin-angiotensin system (RAS) in the clipped kidney plays a critical role in the development of two-kidney, one-clip Goldblatt hypertension (2K1C), but the roles of angiotensin II (Ang II) and AT 1a receptors in the proximal tubules has not been determined previously. The present study tested the hypothesis that genetic deletion of AT 1a receptors selectively in the proximal tubules attenuates the development of 2K1C Goldblatt hypertension via AT 1a receptor-mediated, Na + /H + exchanger 3 (NHE3)-dependent mechanisms. To test the hypothesis, 2K1C Goldblatt hypertension was induced by placing a silver clip, 0.2 mm internal diameter, on the left renal artery for 4 weeks in adult male wild-type (WT), global AT 1a receptor knockout ( Agtr1a -/- ), proximal tubule (PT)-specific Agtr1a -/- (PT- Agtr1a -/- ), or PT- Nhe3 -/- mice, respectively. In WT mice, systolic blood pressure increased in a time-dependent manner reaching a maximal response by Week 3 (Basal: 112 ± 2 vs. 2K1C: 149 ± 4 mmHg, n=12, P <0.01). 2K1C Goldblatt hypertension in WT mice was associated with significant increases in renin mRNA expression in the clipped kidney (Control: 2366 ± 255 vs. Clipped: 3144 ± 569 copies/ng RNA, P <0.01) and decreases in renin mRNA expression in the nonclipped kidney (1738 ± 341 copies/ng RNA, P <0.05). Plasma Ang II levels were significantly increased in WT mice with 2K1C Goldblatt hypertension (Control: 50.2 ± 7.2 vs. 2K1C: 109.7 ± 17.2 pg/ml, P <0.05). Glomerular and tubulointerstitial fibrotic responses were also significantly increased in the clipped kidney ( P <0.01). In contrast to WT mice, the development of 2K1C hypertension was completely attenuated in Agtr1a -/- (Basal: 88 ± 4 vs. 2K1C: 92 ± 2 mmHg, n=9, n.s .), PT- Agtr1a -/- mice (Basal: 101 ± 2 vs. 2K1C: 104 ± 3 mmHg, n=12, n.s .) and PT- Nhe3 -/- mice (Basal: 103 ± 3 vs. 109 ± 5 mmHg, n=12, n.s .). Renin mRNA expression was not different in clipped and nonclipped kidney of Agtr1a -/- mice, but it was decreased in the nonclipped kidney of PT- Agtr1a -/- mice ( P <0.05). Taken together, these data suggest that genetic deletion of AT 1a receptors selectively in the proximal tubules attenuates the development of 2K1C Goldblatt hypertension via AT 1a receptor-mediated, Na + /H + exchanger 3 (NHE3)-dependent mechanisms.

scholarly journals Macrophage-derived IL-6 contributes to ANG II-mediated angiotensinogen stimulation in renal proximal tubular cells

2016 ◽  
Vol 310 (10) ◽  
pp. F1000-F1007 ◽  
Author(s):  
Ryan O'Leary ◽  
Harrison Penrose ◽  
Kayoko Miyata ◽  
Ryousuke Satou
Keyword(s):  
Culture Medium ◽  
Ang Ii ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Ras Activation ◽  
Stat3 Phosphorylation ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Intrarenal Ras ◽  
Renal Proximal Tubular

The development of ANG II-dependent hypertension involves increased infiltration of macrophages (MΦ) and T cells into the kidney and the consequent elevation of intrarenal cytokines including IL-6, which facilitates the progression of hypertension and associated kidney injury. Intrarenal renin-angiotensin system (RAS) activation, including proximal tubular angiotensinogen (AGT) stimulation, has also been regarded as a cardinal mechanism contributing to these diseases. However, the interaction between immune cells and intrarenal RAS activation has not been fully delineated. Therefore, the present study investigated whether ANG II-treated MΦ induce AGT upregulation in renal proximal tubular cells (PTCs). MΦ were treated with 0–10−6 M ANG II for up to 48 h. PTCs were incubated with the collected medium from MΦ. In ANG II-treated MΦ, IL-6 mRNA and protein levels were increased (1.86 ± 0.14, protein level, ratio to control); moreover, IL-6 levels were higher than TNF-α and IL-1β in culture medium isolated from ANG II-treated MΦ. Elevated AGT expression (1.69 ± 0.04, ratio to control) accompanied by phosphorylated STAT3 were observed in PTCs that received culture medium from ANG II-treated MΦ. The addition of a neutralizing IL-6 antibody to the collected medium attenuated phosphorylation of STAT3 and AGT augmentation in PTCs. Furthermore, a JAK2 inhibitor also suppressed STAT3 phosphorylation and AGT augmentation in PTCs. These results demonstrate that ANG II-induced IL-6 elevation in MΦ enhances activation of the JAK-STAT pathway and consequent AGT upregulation in PTCs, suggesting involvement of an immune response in driving intrarenal RAS activity.

Differential regulation of rat glomerular and proximal tubular renin mRNA following uninephrectomy

1996 ◽  
Vol 270 (5) ◽  
pp. F776-F783 ◽  
Author(s):  
J. E. Tank ◽  
O. W. Moe ◽  
R. A. Star ◽  
W. L. Henrich
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin ◽  
Differential Regulation ◽  
Chain Reaction ◽  
Renin Mrna ◽  
Proximal Tubular ◽  
Polymerase Chain ◽  
Single Kidney ◽  
Local Generation ◽  
Secretory Capacity

Angiotensin II is thought to play a role in the renal adaptations to reduced renal mass, but earlier work has shown that plasma renin activity (PRA) does not increase in this setting. To examine this paradox, we studied the effect of uninephrectomy (UNX) on circulating, juxtaglomerular, glomerular, and proximal tubular (PT) renin. PRA was unchanged 2 wk following UNX and fell slightly at 6 wk. Single kidney renin secretory capacity and cortical renin mRNA, reflecting juxtaglomerular renin, were unchanged at 2 and 6 wk. With quantitative competitive reverse transcription-polymerase chain reaction, renin mRNA in microdissected glomeruli and PT were dramatically increased 2 wk post-UNIX (for glomeruli: sham, 1.2 +/- 0.3, vs. UNX, 8.8 +/- 1.9 x 10(5) copies/glomerulus; for PT: sham, 4.6 +/- 0.9, vs. UNX, 17.7 +/- 5.1 x 10(3) copies/mm). By 6 wk, glomerular renin was unchanged, and PT renin mRNA was markedly suppressed (for glomeruli; sham, 2.9 +/- 1.2, vs. UNX, 4.2 +/- 1.1 x 10(5) copies/glomerulus; for PT: sham, 7.5 +/- 2.1, vs. UNX, 1.0 +/- 0.3 x 10(3) copies/mm). These results demonstrate differential regulation of the circulating, juxtaglomerular, glomerular, and PT renin systems. Early activation of glomerular and PT renin may result in increased local generation of angiotensin II and thereby affect renal structural and functional adaptations following UNX.

ANG II-induced downregulation of RBF after a prolonged reduction of renal perfusion pressure is due to pre- and postglomerular constriction

2004 ◽  
Vol 286 (5) ◽  
pp. R865-R873 ◽  
Author(s):  
Charlotte Mehlin Sorensen ◽  
Paul Peter Leyssac ◽  
Max Salomonsson ◽  
Ole Skott ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Perfusion Pressure ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Renal Perfusion Pressure ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Tubular Flow ◽  
Over Time

Previous experiments from our laboratory showed that longer-lasting reductions in renal perfusion pressure (RPP) are associated with a gradual decrease in renal blood flow (RBF) that can be abolished by clamping plasma ANG II concentration ([ANG II]). The aim of the present study was to investigate the mechanisms behind the RBF downregulation in halothane-anesthetized Sprague-Dawley rats during a 30-min reduction in RPP to 88 mmHg. During the 30 min of reduced RPP we also measured glomerular filtration rate (GFR), proximal tubular pressure (Pprox), and proximal tubular flow rate (QLP). Early distal tubular fluid conductivity was measured as an estimate of early distal [NaCl] ([NaCl]ED), and changes in plasma renin concentration (PRC) over time were measured. During 30 min of reduced RPP, RBF decreased gradually from 6.5 ± 0.3 to 6.0 ± 0.3 ml/min after 5 min (NS) to 5.2 ± 0.2 ml/min after 30 min ( P < 0.05). This decrease occurred in parallel with a gradual increase in PRC from 38.2 ± 11.0 × 10-5 to 87.1 ± 25.1 × 10-5 Goldblatt units (GU)/ml after 5 min ( P < 0.05) to 158.5 ± 42.9 × 10-5 GU/ml after 30 min ( P < 0.01). GFR, Pprox, and [NaCl]ED all decreased significantly after 5 min and remained low. Estimates of pre- and postglomerular resistances showed that the autoregulatory mechanisms initially dilated preglomerular vessels to maintain RBF and GFR. However, after 30 min of reduced RPP, both pre- and postglomerular resistance had increased. We conclude that the decrease in RBF over time is caused by increases in both pre- and postglomerular resistance due to rising plasma renin and ANG II concentrations.

Reciprocal feedback regulation of kidney angiotensinogen and renin mRNA expressions by angiotensin II

1992 ◽  
Vol 263 (5) ◽  
pp. E863-E869 ◽  
Author(s):  
H. Schunkert ◽  
J. R. Ingelfinger ◽  
H. Jacob ◽  
B. Jackson ◽  
B. Bouyounes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Feedback Regulation ◽  
Plasma Renin ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Mrna Levels ◽  
Ang Ii ◽  
Plasma Renin Concentration ◽  
Arterial Blood ◽  
Renin Mrna

The present study asks whether angiotensin II (ANG II), a potent inhibitor of renal renin synthesis and release, regulates renal angiotensinogen synthesis. ANG II (or vehicle) was intravenously infused into male Sprague-Dawley rats for 3 days (vehicle or 100, 300, and 1,000 ng.kg-1 x min-1, n = 8/group), significantly increasing mean plasma ANG II concentrations and raising mean arterial blood pressure (MAP). ANG II dose dependently suppressed plasma renin concentration, kidney renin concentration, and renal renin mRNA levels. In contrast, ANG II infusion increased renal angiotensinogen mRNA levels stepwise to 122, 136 (P < 0.05), and 150% (P < 0.05) of control and also increased both liver mRNA levels (P < 0.05) and plasma angiotensinogen concentration (P < 0.05). Three days of angiotensin-converting enzyme inhibition (10 mg.kg-1 x day-1 quinapril in drinking water, n = 8) significantly decreased MAP (P < 0.05) and increased both mean plasma renin concentration (P < 0.05) and renal renin mRNA levels (P < 0.005). Plasma ANG II concentration tended to decrease (not significant), and neither renal nor hepatic angiotensinogen mRNA levels displayed significant difference. However, when data from ANG II-infused and quinapril-treated rats were analyzed together, correlation between plasma ANG II concentrations and renal angiotensinogen mRNA levels was highly significant (P < 0.005, r = 0.585). Thus plasma ANG II upregulates renal angiotensinogen gene expression and downregulates renal renin gene expression, a reciprocal feedback regulation that may have important physiological consequences.

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