Evidence for an intrarenal renin-angiotensin system in the rainbow trout, Oncorhynchus mykiss

2000 ◽  
Vol 278 (6) ◽  
pp. R1685-R1691 ◽  
Author(s):  
J. Anne Brown ◽  
Richard K. Paley ◽  
Shehla Amer ◽  
Stephen J. Aves
Keyword(s):  
Rainbow Trout ◽  
Renin Angiotensin System ◽  
Aortic Pressure ◽  
Vascular Effects ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Molecular Approaches ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Intrarenal Ras

Physiological and molecular approaches were used to investigate the existence of an intrarenal renin-angiotensin system (RAS) in rainbow trout. Inhibition of angiotensin-converting enzyme by captopril (5 × 10− 4 M) rapidly decreased vascular resistance of the trunk of the trout, perfused at 19 mmHg, resulting in an increased perfusate flow rate and a decreased intrarenal dorsal aortic pressure. A profound diuresis occurred in the in situ perfused kidney and reflected both increased glomerular filtration rates and decreased water reabsorption (osmolyte reabsorption was unchanged). Renal and vascular parameters recovered once captopril treatment was stopped. Diuretic and vascular effects of captopril on the in situ trout kidney concur with an inhibition of known vasoconstrictor and antidiuretic actions of angiotensin II. However, at a higher perfusion pressure (28 mmHg), captopril had no effect on intrarenal aortic pressure or perfusate and urine flow rates, suggesting that the trout intrarenal RAS is activated by low perfusion pressures/flows. Existence of the renal RAS in trout was further supported by evidence for angiotensinogen gene expression in kidney as well as liver.

Abstract 227: The Protective Effect of Kidney-Specific ACE Inhibition Against Chronic Angiotensin II Infusions is Associated with Blunted Intrarenal Renin-Angiotensin System Activation

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Jorge F Giani ◽  
Tea Djandjoulia ◽  
Nicholas Fetcher ◽  
Sebastien Fuchs ◽  
Dale M Seth ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Fold Increase ◽  
Ace Inhibition ◽  
Sham Operation ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Intrarenal Ras ◽  
Failed Induction

Introduction: The responses to chronic angiotensin (Ang) II infusions of gene-targeted mice lacking kidney angiotensin-converting enzyme (ACE), in terms of intrarenal Ang II accumulation, hypertension, sodium and water retention are all blunted or absent. The objective of this study was to determine if these reduced responses were associated with changes in the intrarenal renin-angiotensin system (RAS). METHODS: Mice lacking intrarenal ACE (ACE10/10) were generated by targeted homologous recombination placing the expression of ACE only in macrophages. As a result, these mice have normal circulating ACE levels, but no kidney ACE. Wild-type (WT) mice of the same background (C57Bl/J) served as controls. Mice were subjected to sham-operation or subcutaneous infusion of Ang II for two weeks (n=6-10, 400 ng/kg/min via osmotic minipump). Mean arterial pressure (MAP) was followed by telemetry. At the end of the experiment, the kidneys were collected for analysis. Ang II content was measured by RIA. Renal abundance of ACE, angiotensinogen (AGT) and Ang II receptor type 1 (AT1R) were determined by Western Blot in total kidney homogenates. Results: At baseline, the MAP of WT and ACE 10/10 mice was similar 110 ± 4 mmHg vs. 109 ± 3 mmHg respectively (p>0.05). However, when subjected to chronic Ang II infusions, the hypertensive response was blunted in ACE 10/10 mice (129 ± 6 mmHg) vs. WT (146 ± 5 mmHg; P<0.05). Also, intrarenal Ang II accumulation was lower in ACE10/10 mice (724 ± 81 fmol/g) vs. WT (1130 ± 105 fmol/g, p<0.05). In non-treated mice, intrarenal RAS components analysis revealed that the absence of ACE in ACE10/10 mice was accompanied by a significant reduction in AGT (0.41 ± 0.06) and increased AT1R expression (1.32 ± 0.05) when compared to WT (normalized to 1.00, p<0.05 in both instances). Importantly, after chronic Ang II infusions, AGT, ACE and AT1R expression increased in WT (1.36, 1.26 and 1.17 fold increase respectively compared to non-treated WT, p<0.05) but not in the ACE10/10 mice (1.19, 1.06, 0.89 fold increase respectively compared to non-treated ACE10/10, p>0.05). Conclusion: The blunted hypertension and Ang II accumulation of mice devoid of kidney ACE in response to Ang II infusions is associated with a failed induction of renal AGT and the AT1R.

Abstract P613: Absolute Gene Quantification Of Intrarenal Renin-angiotensin System Components Using Droplet Digital PCR Analysis

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Ryousuke Satou ◽  
Akemi Katsurada ◽  
Kayoko Miyata ◽  
Andrei Derbenev ◽  
Andrea Zsombok
Keyword(s):  
Copy Number ◽  
System Analysis ◽  
Renin Angiotensin System ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Gene Copy ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Copy Numbers ◽  
Intrarenal Ras

The intrarenal renin-angiotensin system (RAS) has been shown to play crucial roles in the development of hypertension and RAS associated kidney injury including diabetic nephropathy. Although some circulating RAS components are filtered into kidneys and contribute to the regulation of intrarenal RAS activity, evaluating expression levels of RAS components in the kidney is important to elucidate the mechanisms underlying intrarenal RAS activation. Digital PCR is a new technique that has been established to quantify absolute target gene levels, which allows for comparisons of different gene levels. Thus, this study was performed to establish profiles of absolute gene copy numbers for intrarenal RAS components in wild-type (WT) rats, WT and streptozotocin (STZ)-induced diabetic mice. Male Sprague-Dawley rats (N=5) and male C57BL/6J mice were used in this study. The mice were subjected to either control (N=5) or STZ (200 mg/kg, N=4) injection. Seven days after STZ injection, copy numbers of renal cortical angiotensinogen (AGT), angiotensin-converting enzyme (ACE), ACE2, angiotensin type 1 receptor a (AT1a), and AT2 mRNA were determined by a droplet digital PCR. Since (pro)renin proteins produced by juxtaglomerular cells are secreted to circulating system, analysis of renin mRNA was excluded from this evaluation. In the renal cortex of WT rats, the copy number of AGT was higher than other measured RAS components (AGT: 719.2±46.6, ACE: 116.0±14.9, ACE2: 183.6±21.5, AT1a: 196.0±25.2 copies in 1 ng total RNA). AT2 levels were lower than other components (0.068±0.01 copies). In WT mice, ACE exhibited the highest copy number in the components (AGT: 447.2±29.0, ACE: 1662.4±61.2, ACE2: 676.8±41.5, AT1a: 867.0±16.8, AT2: 0.049±0.01 copies). Although STZ-induced diabetes did not change ACE2 and AT1a, ACE levels were reduced (765.5±98.1 copies) and AT2 levels were augmented (0.10±0.01 copies) as previously demonstrated. Accordingly, the absolute quantification by digital PCR established precise gene profiles of intrarenal RAS components, which will provide rationales for targeting the each component in future studies. Furthermore, the results indicate that the high sensitive assay accurately quantifies rare target genes including intrarenal AT2.

Role of adrenal renin-angiotensin system in the control of aldosterone secretion in sodium-restricted rats

2000 ◽  
Vol 278 (6) ◽  
pp. E1027-E1030 ◽  
Author(s):  
Giuseppina Mazzocchi ◽  
Ludwik K. Malendowicz ◽  
Anna Markowska ◽  
Giovanna Albertin ◽  
Gastone G. Nussdorfer
Keyword(s):  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Zona Glomerulosa ◽  
Normal Diet ◽  
Angiotensin Ii Receptor ◽  
Aldosterone Secretion ◽  
Angiotensin System ◽  
Renin Angiotensin

This study examined the effect of the pharmacological manipulation of adrenal renin-angiotensin system (RAS) on aldosterone secretion from in situ perfused adrenals of rats kept on a normal diet and sodium restricted for 14 days. Neither the angiotensin-converting enzyme inhibitor captopril nor the nonselective angiotensin II receptor antagonist saralasin and the AT1 receptor-selective antagonist losartan affected basal aldosterone output in normally fed rats. In contrast, they concentration dependently decreased aldosterone secretion in sodium-restricted animals, with maximal effective concentration ranging from 10− 7 to 10− 6 M. Captopril (10− 6 M), saralasin (10− 6 M), and losartan (10− 7 M) counteracted aldosterone response to 10 mM K+ in sodium-restricted rats but not in normally fed animals. Collectively, these findings provide evidence that adrenal RAS plays a role in the regulation of aldosterone secretion, but only under conditions of prolonged stimulation of zona glomerulosa probably leading to overexpression of adrenal RAS.

scholarly journals Vascular Effects of ACE Inhibition Independent of the Renin-Angiotensin System in Hypertensive Renovascular Disease

Hypertension ◽  
2001 ◽  
Vol 37 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Jacobine M. A. van Ampting ◽  
Michel L. Hijmering ◽  
Jaap J. Beutler ◽  
Ronald E. van Etten ◽  
Hein A. Koomans ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Renovascular Disease ◽  
Vascular Effects ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Mediation of humoral catecholamine secretion by the renin-angiotensin system in hypotensive rainbow trout (Oncorhynchus mykiss)

1999 ◽  
Vol 160 (3) ◽  
pp. 351-363 ◽  
Author(s):  
NJ Bernier ◽  
H Kaiya ◽  
Y Takei ◽  
SF Perry
Keyword(s):  
Blood Pressure ◽  
Rainbow Trout ◽  
Enzyme Inhibitor ◽  
Plasma Concentrations ◽  
Plasma Catecholamines ◽  
Renin Angiotensin System ◽  
Adrenergic System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines.

scholarly journals ELABELA antagonizes intrarenal renin-angiotensin system to lower blood pressure and protects against renal injury

2020 ◽  
Vol 318 (5) ◽  
pp. F1122-F1135 ◽  
Author(s):  
Chuanming Xu ◽  
Fei Wang ◽  
Yanting Chen ◽  
Shiying Xie ◽  
Danielle Sng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Protein Expression ◽  
Collecting Duct ◽  
Protective Action ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Distal Nephron ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Intrarenal Ras

Emerging evidence has demonstrated that (pro)renin receptor (PRR)-mediated activation of intrarenal renin-angiotensin system (RAS) plays an essential role in renal handling of Na+ and water balance and blood pressure. The present study tested the possibility that the intrarenal RAS served as a molecular target for the protective action of ELABELA (ELA), a novel endogenous ligand of apelin receptor, in the distal nephron. By RNAscope and immunofluorescence, mRNA and protein expression of endogenous ELA was consistently localized to the collecting duct (CD). Apelin was also found in the medullary CDs as assessed by immunofluorescence. In cultured CD-derived M1 cells, exogenous ELA induced parallel decreases of full-length PRR (fPRR), soluble PRR (sPRR), and prorenin/renin protein expression as assessed by immunoblotting and medium sPRR and prorenin/renin levels by ELISA, all of which were reversed by 8-bromoadenosine 3′,5′-cyclic monophosphate. Conversely, deletion of PRR in the CD or nephron in mice elevated Apela and Apln mRNA levels as well as urinary ELA and apelin excretion, supporting the antagonistic relationship between the two systems. Administration of exogenous ELA-32 infusion (1.5 mg·kg−1·day−1, minipump) to high salt (HS)-loaded Dahl salt-sensitive (SS) rats significantly lowered mean arterial pressure, systolic blood pressure, diastolic blood pressure, and albuminuria, accompanied with a reduction of urinary sPRR, angiotensin II, and prorenin/renin excretion. HS upregulated renal medullary protein expression of fPRR, sPRR, prorenin, and renin in Dahl SS rats, all of which were significantly blunted by exogenous ELA-32 infusion. Additionally, HS-induced upregulation of inflammatory cytokines ( IL-1β, IL-2, IL-6, IL-17A, IFN-γ, VCAM-1, ICAM-1, and MCP-1), fibrosis markers ( TGF-β1, FN, Col1A1, PAI-1, and TIMP-1), and kidney injury markers ( NGAL, Kim-1, albuminuria, and urinary NGAL excretion) were markedly blocked by exogenous ELA infusion. Together, these results support the antagonistic interaction between ELA and intrarenal RAS in the distal nephron that appears to exert a major impact on blood pressure regulation.

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