scholarly journals Quantification of conversion and degradation of circulating angiotensin in rats

1999 ◽  
Vol 277 (2) ◽  
pp. R412-R418 ◽  
Author(s):  
Johannes Bauer ◽  
Heike Berthold ◽  
Franz Schaefer ◽  
Heimo Ehmke ◽  
Niranjan Parekh
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Systemic Circulation ◽  
Left Renal Artery ◽  
Minor Importance ◽  
Ang Ii ◽  
Renal Circulation ◽  
Degradation Rates ◽  
Measured Change

The aim of the present study was to quantify with a uniform technique the rates of conversion of ANG I to ANG II in the lung and kidney and the degradation of both peptides to biologically inactive products in the pulmonary, renal, and systemic circulation. We infused the peptides intravenously, into the left ventricle, and into the left renal artery of rats and compared their effects on renal blood flow. The measured change in renal blood flow was used as a bioassay parameter to estimate the concentration of circulating ANG II. Mathematical analysis of our data allowed us to calculate conversion and degradation rates. Furthermore, the role of aminopeptidases A (EC 3.4.11.7 ) and N (EC 3.4.11.2 ) in the degradation of the peptides in the kidney was investigated by intrarenal infusion of the inhibitor amastatin. Our results show that the conversion rate of ANG I is 75% in the pulmonary and 21% in the renal circulation. Both peptides are degraded by 5% in the pulmonary, by 67% in the systemic, and by 93% in the renal circulation. Amastatin prevented 60% of the renal degradation of the peptides to inactive products, and this effect could be attributed to inhibition of aminopeptidase N. The results indicate that the converting capacity of the kidney is of minor importance for endocrine generation of ANG II but could be useful for the paracrine production.

scholarly journals Gender Difference in Renal Blood Flow Response to Angiotensin II Administration after Ischemia/Reperfusion in Rats: The Role of AT2 Receptor

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Maryam Maleki ◽  
Mehdi Nematbakhsh
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Female Rats ◽  
Male Rats ◽  
Ang Ii ◽  
The Impact

Background. Renal ischemia/reperfusion (I/R) is one of the major causes of kidney failure, and it may interact with renin angiotensin system while angiotensin II (Ang II) type 2 receptor (AT2R) expression is gender dependent. We examined the role of AT2R blockade on vascular response to Ang II after I/R in rats.Methods.Male and female rats were subjected to 30 min renal ischemia followed by reperfusion. Two groups of rats received either vehicle or AT2R antagonist, PD123319. Mean arterial pressure (MAP), and renal blood flow (RBF) responses were assessed during graded Ang II (100, 300, and 1000 ng/kg/min, i.v.) infusion at controlled renal perfusion pressure (RPP).Results.Vehicle or antagonist did not alter MAP, RPP, and RBF levels significantly; however, 30 min after reperfusion, RBF decreased insignificantly in female treated with PD123319 (P=0.07). Ang II reduced RBF and increased renal vascular resistance (RVR) in a dose-related fashion (Pdose<0.0001), and PD123319 intensified the reduction of RBF response in female (Pgroup<0.005), but not in male rats.Conclusion.The impact of the AT2R on vascular responses to Ang II in renal I/R injury appears to be sexually dimorphic. PD123319 infusion promotes these hemodynamic responses in female more than in male rats.

Vasoconstrictor-induced changes in renal blood flow: role of prostaglandins and histamine

1988 ◽  
Vol 254 (4) ◽  
pp. F470-F476 ◽  
Author(s):  
R. O. Banks
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Histidine Decarboxylase ◽  
Reactive Hyperemia ◽  
Constant Infusion ◽  
Base Line ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Control Value

The role of histamine (H) and prostaglandins (PGs) in the renal vasoconstriction prompted by a 10-min intrarenal infusion of norepinephrine (NE, 0.2 micrograms), antidiuretic hormone (ADH, 10 mU), or angiotensin II (ANG II, 0.05 micrograms) was evaluated in anesthetized dogs (amounts are per min per kg). Renal blood flow (RBF, flow probe) decreased four- to fivefold during the 1st min of infusion with each agonist but then gradually returned toward base line. This “escape” was greatest with ADH, less with NE, and small with ANG II. There was a postinfusion reactive hyperemia (RH) only after NE; NE-RH was 4.26 +/- 0.75 (SE) ml/g. Meclofenamate (MFA) reduced NE-RH to 60 +/- 11% of control and decreased NE escape. The H1-receptor antagonist, chlorpheniramine (CP), decreased NE-RH to 24 +/- 5% of control and reduced NE escape. MFA slowed, but did not block, ADH escape and had little effect on ANG II escape. CP did not affect ADH or ANG II escape. The histidine decarboxylase inhibitor, p-toluenesulfonohydrazine, did not affect NE escape but decreased NE-RH to 22 +/- 6% of control. Bolus injections of ADH during a constant infusion of the hormone were not vasoactive, indicating a tachyphylaxis-like phenomenon; this was not found with ANG II or NE. Finally, the excretion of histamine-like material increased from a control value of 0.69 +/- 0.08 to 1.28 +/- 0.28 micrograms/min during NE-RH. These results indicate that NE releases histamine and PGs from the kidney and that PGs account, primarily, for NE escape, whereas histamine accounts, primarily, for NE-RH.

Effects of endothelin on renal function in dogs and rats

1990 ◽  
Vol 258 (4) ◽  
pp. F775-F780 ◽  
Author(s):  
R. O. Banks
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Function ◽  
Renal Blood Flow ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Left Renal Artery ◽  
Ang Ii ◽  
Arterial Blood ◽  
Entire Experiment

Endothelin was infused for 20 min into the left renal artery of pentobarbital-anesthetized dogs at 1 (n = 6) and 10 (n = 5) ng.min-1.kg-1. Renal blood flow (flow probe) increased 6 +/- 2 (SE) and 29 +/- 2% during the first 5 min of endothelin infusion and then slowly decreased to 86 +/- 3 and 29 +/- 2% of control at 20 min, respectively; the low renal blood flow persisted for at least 30 min after endothelin infusion, and there were no systemic effects of the peptide at either dose. These effects of endothelin on renal function were not altered by the angiotensin (ANG) II receptor antagonist, [Sar1,Thr8]ANG II. In the rat, endothelin was infused intravenously into three groups of pentobarbital-anesthetized females for 30 min at 0.1 microgram.min-1.kg-1; five had endothelin only, six had either endothelin + [Sar1,Thr8]ANG II (n = 4, 1.0 micrograms.min-1.kg-1) or endothelin + saralasin (n = 2, 1 and 2 micrograms.kg-1.min-1), and five had endothelin + captopril (5 mg.h-1.kg-1). The inhibitors were infused throughout the entire experiment. During infusion of endothelin alone mean arterial blood pressure increased from 106 +/- 2 to 136 +/- 4 mmHg and the glomerular filtration rate decreased from 2.7 +/- 0.2 to 0.7 +/- 0.3 ml/min. Captopril attenuated the endothelin-induced changes in renal function but not the increase in mean arterial blood pressure, whereas the competitive ANG II receptor antagonists had no effect on either the systemic or renal actions of the peptide. These data demonstrate that endothelin is a potent renal vasoconstrictor with transient vasodilator effects and that the inhibition of kinin degradation may attenuate the renal actions of the peptide.

scholarly journals Angiotensin 1-7 Administration Increases Renal Blood Flow in the Absence of Bradykinin B2 Receptor in Ovariectomized Estradiol Treated Rats: The Role of Mas Receptor

2019 ◽  
Author(s):  
Shadan Saberi ◽  
Aghdas Dehghani ◽  
Mehdi Nematbakhsh
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Ovariectomized Rats ◽  
Vehicle Group ◽  
Estradiol Valerate ◽  
Bradykinin B2 Receptor ◽  
Hoe 140 ◽  
Group 2 ◽  
Renal Vascular

Abstract- Renin angiotensin (RAS), kallikrein kinin (KKS), and sex hormonal systems demonstrate a complex contribution in kidney circulation. This study was designed to investigate the role of angiotensin 1-7 (Ang 1-7) receptor (MasR) and of bradykinin B2 receptor (B2R) in renal blood flow (RBF) response to Ang 1-7 infusion in ovariectomized estradiol treated rats. The ovariectomized rats received intramuscular vehicle (group 1, OV) or estradiol valerate (500 µg/Kg/week) (group 2, OVE) for two weeks. Then each group was divided into two subgroups subjected to receive B2R antagonist (HOE-140, subgroup A), or MasR antagonist (A779) plus HOE-140 (subgroup B). RBF and renal vascular resistance (RVR) responses to graded Ang 1-7 infusion were determined. In condition of B2R alone blocking, RBF response to Ang 1-7 in OVE group was significantly greater than that of OV group (P=0.05), however this response difference was failed by co-blockades of MasR and B2R. Estradiol could promote RBF response to graded Ang 1-7 infusion in the absence of B2R alone, however when both receptors (MasR and B2R) were blocked the role of estradiol was limited.

Abstract P141: GYY4137, a H 2 S Donor, Normalizes miR-132 Targeted Sirt1 and Ace2 Expression to Improve Kidney Function in Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Gregory Weber ◽  
Sathnur Pushpakumar ◽  
Utpal Sen
Keyword(s):  
Blood Flow ◽  
Kidney Function ◽  
Expression Patterns ◽  
Sirtuin 1 ◽  
Ang Ii ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Epigenetic Gene Silencing ◽  
Increased Blood Flow

MicroRNAs regulate several physiological processes and are implicated in various pathologies, including hypertension. Previous work indicates miR-132 targets Sirtuin 1 (Sirt1), a histone deacetylase and regulator of epigenetic gene silencing in various cellular processes. Sirt1 is expressed in the kidney; however, its role in hypertensive kidney and whether it is regulated by physiological gaseous molecules, such as hydrogen sulfide (H 2 S), is not known. In this study, we sought to determine the role of miR-132 in regulating Sirt1, Ace2 and At1 in hypertensive kidney and whether H 2 S donor, GYY4137 (GYY), could reverse these effects and mitigates renal dysfunction. Wild-type mice were treated without or with Ang-II (1000 ng/Kg/Min) and GYY (133 μM) for 4 weeks. Quantitative PCR, Western blot, and immunofluorescence assays were performed. Increased expression levels of miR-132 in hypertensive mice (3.79 fold vs control) were reduced in mice receiving GYY treatment (2.43 fold vs control). Sirt1 expression was reduced (-1.15 fold) in Ang-II mice but was upregulated in GYY (1.25 fold) and Ang-II+GYY (1.9 fold) groups. A similar effect was seen with Sirt1 protein where the expression was increased in animals treated with GYY and Ang-II+GYY (1.16, 1.03 respectively) compared to Ang-II (0.47). Ace2 in Ang-II+GYY (0.45) was increased compared to Ang-II (0.17), while At1 was reduced (0.46) compared to Ang-II (0.86). Immunofluorescence showed decreased signal of Sirt1 in the glomerulus in Ang-II mice and increased At1 in the blood vessels surrounding the glomerulus, leading to constriction of renal artery, decreased blood flow, and kidney dysfunction. These effects were alleviated in mice treated with GYY. Our data suggests that upregulation of miR-132 in hypertensive kidney decreases Sirt1 and Ace2 expression, leading to increased Ang-II signaling through the At1 receptor and GYY supplementation reverses these expression patterns, leading to increased blood flow and kidney function.

Abstract 062: Regulation of Nephron Afferent Arteriole Resistance in Obesity: Role of Connecting Tubule Glomerular Feedback

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sumit R Monu ◽  
Mani Maheshwari ◽  
Hong Wang ◽  
Ed Peterson ◽  
Oscar Carretero
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Tubuloglomerular Feedback ◽  
Afferent Arteriole ◽  
Connecting Tubule ◽  
Single Nephron ◽  
Renal Micropuncture ◽  
The Difference

In obesity, renal damage is caused by increase in renal blood flow (RBF), glomerular capillary pressure (P GC ), and single nephron glomerular filtration rate but the mechanism behind this alteration in renal hemodynamics is unclear. P GC is controlled mainly by the afferent arteriole (Af-Art) resistance. Af-Art resistance is regulated by mechanism similar to that in other arterioles and in addition, it is regulated by two intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to an increase in sodium chloride (NaCl) in the macula densa, via sodium–potassium-2-chloride cotransporter-2 (NKCC2) and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation and is mediated by connecting tubule via epithelial sodium channel (ENaC). CTGF is blocked by the ENaC inhibitor benzamil. Attenuation of TGF reduces Af-Art resistance and allows systemic pressure to get transmitted to the glomerulus that causes glomerular barotrauma/damage. In the current study, we tested the hypothesis that TGF is attenuated in obesity and that CTGF contributes to this effect. We used Zucker obese rats (ZOR) while Zucker lean rats (ZLR) served as controls. We performed in-vivo renal micropuncture of individual rat nephrons while measuring stop-flow pressure (P SF ), an index of P GC. TGF response was measured as a decrease in P SF induced by changing the rate of late proximal perfusion from 0 to 40nl/min in stepwise manner.CTGF was calculated as the difference of P SF value between vehicle and benzamil treatment, at each perfusion rate. Maximal TGF response was significantly less in ZOR (6.16 ± 0.52 mmHg) when compared to the ZLR (8.35 ± 1.00mmHg), p<0.05 , indicating TGF resetting in the ZOR. CTGF was significantly higher in ZOR (6.33±1.95 mmHg) when compared to ZLR (1.38±0.89 mmHg), p<0.05 . When CTGF was inhibited with the ENaC blocker Benzamil (1μM), maximum P SF decrease was 12.30±1.72 mmHg in ZOR and 10.60 ± 1.73 mmHg in ZLR, indicating that blockade of CTGF restored TGF response in ZOR. These observations led us to conclude that TGF is reset in ZOR and that enhanced CTGF contributes to this effect. Increase in CTGF may explain higher renal blood flow, increased P GC and higher glomerular damage in obesity.

THE ROLE OF INCREASED SYMPATHETIC NERVOUS ACTIVITY FOR THE REDUCED RENAL BLOOD FLOW IN PATIENTS WITH CIRRHOSIS

1981 ◽  
Vol 1 (s1) ◽  
pp. 71-75 ◽  
Author(s):  
Helmer Ring-Larsen ◽  
Jens H. Henriksen ◽  
Birger Hesse ◽  
Niels Juel Christensen
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Sympathetic Nervous

Splanchnic blood flow and hepatic glucose production in exercising humans: role of renin-angiotensin system

2001 ◽  
Vol 281 (6) ◽  
pp. R1854-R1861 ◽  
Author(s):  
Raynald Bergeron ◽  
Michael Kjær ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
Dorthe Skovgaard ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renin Angiotensin System ◽  
Glucose Production ◽  
Splanchnic Blood Flow ◽  
Control Group ◽  
Moderate Exercise ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (V˙o 2 max) followed by 30 min at 70% V˙o 2 maxeither with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ∼20-fold increase ( P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, V˙o 2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.

Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat

2001 ◽  
Vol 281 (6) ◽  
pp. F1132-F1140 ◽  
Author(s):  
R. Kramp ◽  
P. Fourmanoir ◽  
N. Caron
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Receptor Subtypes ◽  
Receptor Blockade ◽  
Flow Probe ◽  
Relative Contribution ◽  
No Inhibition ◽  
Electromagnetic Flow Probe ◽  
Bq 610

First published August 15, 2001; 10.1152/ajprenal.00078.2001.—Renal blood flow (RBF) autoregulatory efficiency may be enhanced during NO inhibition in the rat, as recently reported. Under these conditions, endothelin (ET) synthesis and release may be increased. Our purpose was therefore to determine the role of ET in RBF autoregulatory changes induced by NO inhibition. To address this point, ETA/B receptors were blocked in anesthetized rats with bosentan, or selectively with BQ-610 or BQ-788. NO synthesis was inhibited with N G-nitro-l-arginine methyl ester (l-NAME). Mean arterial pressure (MAP) was decreased after bosentan (−10 mmHg; P < 0.01) or increased after l-NAME (25 mmHg; P < 0.001). RBF measured with an electromagnetic flow probe was reduced byl-NAME (−50%) and by BQ-788 (−24%). The pressure limits of the autoregulatory plateau (PA ∼100 mmHg) and of no RBF autoregulation (Po ∼80 mmHg) were significantly lowered by 15 mmHg after l-NAME but were unchanged after bosentan, BQ-610, or BQ-788. During NO inhibition, autoregulatory resetting was completely hindered by bosentan (PA ∼100 mmHg) and by ETB receptor blockade with BQ-788 (PA ∼106 mmHg), but not by ETA receptor blockade with BQ-610 (PA ∼85 mmHg). These results suggest that the involvement of ET in the RBF autoregulatory resetting occurs during NO inhibition, possibly by preferential activation of the ETB receptor. However, the relative contribution of ET receptor subtypes remains to be further specified.

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