Generation of angiotensin II from human plasma by tissue kallikrein

1992 ◽  
Vol 83 (4) ◽  
pp. 477-482 ◽  
Author(s):  
N. Krivoy ◽  
H. Schlüter ◽  
M. Karas ◽  
W. Zidek
Keyword(s):  
Angiotensin Ii ◽  
Molecular Mass ◽  
Human Plasma ◽  
Rat Kidney ◽  
Ionization Mass ◽  
Tissue Kallikrein ◽  
Porcine Pancreas ◽  
Physiological Conditions ◽  
Perfused Rat Kidney ◽  
Vasopressor Activity

1. Human plasma was incubated with tissue kallikrein from porcine pancreas, dialysed to obtain a fraction with a molecular mass < 10 kDa and further purified by reverse-phase chromatography. 2. Vasopressor activity in the fractions obtained was tested in the isolated perfused rat kidney. 3. In one fraction a strong vasopressor action was found, which was blocked by saralasin and by an angiotensin II antibody. 4. Aprotinin inhibited the formation of vasopressor substances by tissue kallikrein. 5. U.v.-laser desorption/ionization mass spectrometry revealed a molecular mass of 1046 Da in the purified active fraction. 6. It is concluded that tissue kallikrein forms not only kinins, but also angiotensin II, from human plasma under physiological conditions.

Effect of exogenous and endogenous angiotensin II in the isolated perfused rat kidney

1978 ◽  
Vol 235 (6) ◽  
pp. F605-F610 ◽  
Author(s):  
M. Davalos ◽  
N. S. Frega ◽  
B. Saker ◽  
A. Leaf
Keyword(s):  
Angiotensin Ii ◽  
Driving Force ◽  
Constant Pressure ◽  
Enzyme Inhibitor ◽  
Rat Kidney ◽  
Filtration Fraction ◽  
Renin Substrate ◽  
Perfusate Flow ◽  
Perfused Rat Kidney ◽  
The Face

Rat kidneys were perfused with an artificial solution at constant pressure. The infusion of angiotensin II (AII) (1.5––6 ng min-1) reduced renal perfusate flow (RPF) from 36.6 +/- 2.4 to 19.3 +/- 1.4 ml min-1 (P less than 0.001) (n = 13); GFR rose from 0.48 +/- 0.06 to 0.63 +/- 0.04 ml min-1 (P less than 0.05), and filtration fraction (FF) rose accordingly from 0.015 +/- 0.002 to 0.033 +/- 0.003 (P greater than 0.01). The same results were obtained with purified renin substrate (synthetic tetradecapeptide, 100 ng min-1, n = 8); RPF fell from 31.5 +/- 2.9 to 17.2 +/- 2 ml min-1 (P less than 0.001), GFR rose from 0.36 +/- 0.05 to 0.51 +/- 0.04 ml min-1 (P less than 0.05), and FF increased from 0.021 +/- 0.002 to 0.034 +/- 0.006 (P less than 0.01). The effects of renin substrate were completely prevented by the converting enzyme inhibitor SQ 20,881 (3 X 10(-5) M). In another six experiments the effects of renin substrate at the same dose were fully reversed by addition of the analogue [Sar1,Ala8]AII. We interpret these findings to indicate that both exogenous and endogenous AII produce preferential vasoconstriction of the efferent arteriole, increasing the driving force for ultrafiltration and thereby maintaining or increasing GFR in the face of a reduced plasma flow.

The Effect of Angiotensin upon the Vasculature of the Isolated Perfused Rat Kidney

1974 ◽  
Vol 46 (5) ◽  
pp. 647-650
Author(s):  
R. B. Cross ◽  
J. W. Trace ◽  
J. R. Vattuone
Keyword(s):  
Angiotensin Ii ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Total Flow ◽  
Renal Vasculature ◽  
Low Concentrations ◽  
Perfused Rat Kidney ◽  
Renal Flow ◽  
Intrarenal Distribution ◽  
Isolated Rat

1. The effect of angiotensin II-amide upon the intrarenal distribution of perfusate was studied in the isolated rat kidney. 2. Low concentrations of angiotensin, 4·86 pmol/l (0·005 μg/l), reduced the flow rate through the papilla but did not alter total flow. 3. Higher concentrations of angiotensin, 0·486 nmol/l (0·5 μg/l), reduced total renal flow but did not decrease papillary perfusion. 4. In these experiments the perfusion pressure was maintained constant, indicating that the changes in flow were due to a direct effect of angiotensin upon the renal vasculature.

DuP 753 Is a Potent Nonpeptide Antagonist of Angiotensin II Receptors in Isolated Perfused Rat Kidney and Cultured Renal Cells

1991 ◽  
Vol 4 (4_Pt_2) ◽  
pp. 303S-308S ◽  
Author(s):  
Beatriz M.A. Fontoura ◽  
Daniel R. Nussenzveig ◽  
Pieter B.M.W.M. Timmermans ◽  
Thomas Maack
Keyword(s):  
Angiotensin Ii ◽  
Rat Kidney ◽  
Angiotensin Ii Receptors ◽  
Renal Cells ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

scholarly journals Purification and characterization of angiotensin II AT2 receptors from neonatal rat kidney

1993 ◽  
Vol 90 (23) ◽  
pp. 11009-11013 ◽  
Author(s):  
G M Ciuffo ◽  
F M Heemskerk ◽  
J M Saavedra
Keyword(s):  
Angiotensin Ii ◽  
Molecular Mass ◽  
Isoelectric Point ◽  
Rat Kidney ◽  
Neonatal Rat ◽  
Affinity Column ◽  
Homogeneous State ◽  
Ang Ii ◽  
Soluble Extract ◽  
At2 Receptors

Angiotensin II (Ang II) AT2 receptors were purified 40,000-fold to a nearly homogeneous state after solubilization from neonatal rat kidney membranes with 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propane-sulfonic acid. Comparable IC50 values for the soluble extract (0.32 nM) and membranes (0.31 nM) were obtained by competition curves with 125I-labeled CGP42112, a selective AT2 ligand. Binding to AT2 receptors in the soluble extract was not sensitive to dithiothreitol. AT2 receptors were further purified by gel filtration and a CGP42112 Sepharose affinity column. Ang II AT2 receptors were selectively eluted with 5 microM CGP42112 at 4 degrees C, and a single band with an apparent molecular mass of 71 kDa was obtained after SDS/PAGE. Two-dimensional electrophoresis confirmed the purity of the protein and an isoelectric point of 5.3-5.5 was obtained. A highly selective elution of the AT2 receptors from the affinity column was performed with 5 nM 125I-labeled CGP42112 at room temperature after the column was treated with 1 microM losartan in the presence of high salt. After cross-linking, a major labeled protein with similar molecular mass and isoelectric point was obtained. Dissociation of the radiolabeled protein was insensitive to losartan but was enhanced by CGP42112, PD123177, Ang II, and [Sar1]Ang II. In summary, Ang II AT2 receptors were purified by CGP42112 affinity chromatography and selective elution and retain the pharmacological specificity of particulate receptors.

Involvement of neutral sphingomyelinase in the angiotensin II signaling pathway

2015 ◽  
Vol 308 (10) ◽  
pp. F1178-F1187 ◽  
Author(s):  
Rocio Bautista-Pérez ◽  
Leonardo del Valle-Mondragón ◽  
Agustina Cano-Martínez ◽  
Oscar Pérez-Méndez ◽  
Bruno Escalante ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Rat Kidney ◽  
Muscle Layer ◽  
Ang Ii ◽  
Renal Vasculature ◽  
Isolated Perfused Rat Kidney ◽  
Renal Vasoconstriction ◽  
Neutral Sphingomyelinase ◽  
Perfused Rat Kidney

The possibility that angiotensin II (ANG II) exerts its effects through the activation of neutral sphingomyelinase (nSMase) has not been tested in kidneys. The results of the present study provide evidence for the activity and expression of nSMase in rat kidneys. In isolated perfused rat kidney, ANG II-induced renal vasoconstriction was inhibited by GW4869, an inhibitor of nSMase. We used nSMase for investigating the signal transduction downstream of ceramide. nSMase constricted the renal vasculature. An inhibitor of ceramidase (CDase), N-oleoylethanolamine (OEA), enhanced either ANG II- or nSMase-induced renal vasoconstriction. To demonstrate the interaction between the nSMase and cytosolic phospholipase A2 (cPLA2) signal transduction pathways, we evaluated the response to nSMase in the presence and absence of inhibitors of arachidonic acid (AA) metabolism: arachidonyl trifluoromethyl ketone (AACOCF3), an inhibitor of cPLA2; 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of all AA pathways; indomethacin, an inhibitor of cyclooxygenase (COX); furegrelate, a thromboxane A2 (TxA2)-synthase inhibitor; and SQ29548 , a TxA2-receptor antagonist. In these experiments, the nSMase-induced renal vasoconstriction decreased. ANG II or nSMase was associated with an increase in the release of thromboxane B2 (TxB2) in the renal perfusate of isolated perfused rat kidney. In addition, the coexpression of the ceramide with cPLA2, was found in the smooth muscle layer of intrarenal vessels. Our results suggest that ANG II stimulates ceramide formation via the activation of nSMase; thus ceramide may indirectly regulate vasoactive processes that modulate the activity of cPLA2 and the release of TxA2.

Natriuretic effect of atrial extract on isolated perfused rat kidney

1983 ◽  
Vol 61 (12) ◽  
pp. 1462-1466 ◽  
Author(s):  
A. D. Baines ◽  
A. J. DeBold ◽  
H. Sonnenberg
Keyword(s):  
Sodium Chloride ◽  
Angiotensin Ii ◽  
Rat Kidney ◽  
Free Water ◽  
Free Water Clearance ◽  
Variable Effect ◽  
Water Excretion ◽  
Perfused Rat Kidney ◽  
Natriuretic Effect ◽  
Renal Vascular

To examine the mechanisms underlying the natriuretic action of a partially purified extract of rat atria (AE) we injected the equivalent of one atrium into isolated perfused rat kidneys. Some kidneys received an infusion of angiotensin II at 0.5 ng/min throughout the experiment. In the absence of angiotensin AE had a variable effect on renal vascular resistance (RVR) but, in the presence of angiotensin II, AE consistently decreased RVR by 3% for 5 min followed by a slight increase. Inulin clearance and filtration fraction increased slightly but significantly. AE increased sodium, chloride, phosphate, and free water clearance but not potassium excretion. Ventricular extract had no effect on any of these variables. Furosemide (50–250 μg) increased sodium, chloride, and potassium but not phosphate or free water excretion. AE did not alter dopamine or norepinephrine excretion. We conclude that AE increases the glomerular filtration rate (GFR) and inhibits tubular reabsorption by mechanisms which differ, at least in part, from those affected by furosemide.

scholarly journals RAGE ligands stimulate angiotensin II type I receptor (AT1) via RAGE/AT1 complex on the cell membrane

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Serina Yokoyama ◽  
Tatsuo Kawai ◽  
Koichi Yamamoto ◽  
Huang Yibin ◽  
Hiroko Yamamoto ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Epithelial Cells ◽  
G Protein ◽  
Rat Kidney ◽  
Chinese Hamster ◽  
Cellular Responses ◽  
Type I ◽  
Α Subunit ◽  
Mesenchymal Transition

AbstractThe receptor for advanced glycation end-products (RAGE) and the G protein-coupled angiotensin II (AngII) type I receptor (AT1) play a central role in cardiovascular diseases. It was recently reported that RAGE modifies AngII-mediated AT1 activation via the membrane oligomeric complex of the two receptors. In this study, we investigated the presence of the different directional crosstalk in this phenomenon, that is, the RAGE/AT1 complex plays a role in the signal transduction pathway of RAGE ligands. We generated Chinese hamster ovary (CHO) cells stably expressing RAGE and AT1, mutated AT1, or AT2 receptor. The activation of two types of G protein α-subunit, Gq and Gi, was estimated through the accumulation of inositol monophosphate and the inhibition of forskolin-induced cAMP production, respectively. Rat kidney epithelial cells were used to assess RAGE ligand-induced cellular responses. We determined that RAGE ligands activated Gi, but not Gq, only in cells expressing RAGE and wildtype AT1. The activation was inhibited by an AT1 blocker (ARB) as well as a RAGE inhibitor. ARBs inhibited RAGE ligand-induced ERK phosphorylation, NF-κB activation, and epithelial–mesenchymal transition of rat renal epithelial cells. Our findings suggest that the activation of AT1 plays a central role in RAGE-mediated cellular responses and elucidate the role of a novel molecular mechanism in the development of cardiovascular diseases.

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