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.

Renal hemodynamic responses to increased renal venous pressure: role of angiotensin II

1982 ◽  
Vol 243 (3) ◽  
pp. F260-F264 ◽  
Author(s):  
P. R. Kastner ◽  
J. E. Hall ◽  
A. C. Guyton
Keyword(s):  
Angiotensin Ii ◽  
Filtration Rate ◽  
Enzyme Inhibitor ◽  
Venous Pressure ◽  
Renin Secretion ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Filtration Fraction ◽  
A Value

Studies were performed to quantitate the effects of progressive increases in renal venous pressure (RVP) on renin secretion (RS) and renal hemodynamics. RVP was raised in 10 mmHg increments to 50 mmHg. Renin secretion rate increased modestly as RVP was increased to 30 mmHg and then increased sharply after RVP exceeded 30 mmHg. Glomerular filtration rate (GFR), renal blood flow (RBF), and filtration fraction (FF) did not change significantly when RVP was elevated to 50 mmHg. GFR and RBF were also measured after the renin-angiotension system (RAS) was blocked with the angiotensin converting enzyme inhibitor (CEI) SQ 14225. After a 60-min CEI infusion, RBF was elevated (32%), GFR was unchanged, FF was decreased, and total renal resistance (TRR) was decreased. As RVP was increased to 50 mmHg, GFR and FF decreased to 36.3 and 40.0% of control, respectively, RBF returned to a value not significantly different from control, and TRR decreased to 44.8% of control. The data indicate that the RAS plays an important role in preventing reductions in GFR during increased RVP because blockade of angiotensin II (ANG II) formation by the CEI results in marked decreases in GFR at high RVPs. The decreases in GFR after ANG II blockade and RVP elevation were not due to lack of renal vasodilation, since TRR was maintained below while RBF was maintained either above or at the pre-CEI levels.

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.

Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney

1984 ◽  
Vol 246 (4) ◽  
pp. F447-F456 ◽  
Author(s):  
M. J. Camargo ◽  
H. D. Kleinert ◽  
S. A. Atlas ◽  
J. E. Sealey ◽  
J. H. Laragh ◽  
...  
Keyword(s):  
Perfusion Pressure ◽  
Rat Kidney ◽  
Fractional Excretion ◽  
Electrolyte Excretion ◽  
Renal Vasculature ◽  
Filtration Fraction ◽  
Perfused Rat Kidney ◽  
Site Of Action ◽  
Initial Control ◽  
Renal Vascular

The effects of rat atrial tissue extract on renal hemodynamics and fluid and electrolyte excretion were investigated in the isolated perfused rat kidney (IK). IK were perfused at a constant effective perfusion pressure of about 90 mmHg. After control clearance periods (C), extracts of rat atria (AE) or ventricles (VE) were added to the perfusate and three 10-min experimental periods followed. AE, but not VE, significantly increased (P less than 0.001) renal vascular resistance (RVR) to 133 +/- 8% of C, GFR to 201 +/- 34%, filtration fraction to 245 +/- 41%, urine flow (V) to 675 +/- 131%, fractional excretion (FE) of H2O to 336 +/- 29%, absolute Na excretion (UNaV) to 1,259 +/- 290%, FENa to 642 +/- 129%, UKV to 2,226 +/- 1,237%, and FEK to 542 +/- 119%. Despite the marked natriuresis, since GFR doubled, Na reabsorption rose from 78.3 +/- 36.3 in C to 132 +/- 36.3 mueq/min after AE. The effects of AE were immediate and lasted to the end of the perfusion. The lower the initial control GFR, the larger was the AE-induced increase in GFR. Perfusion with low [Ca] (0.2 mM) or verapamil (10(-5) M) severely blunted the hemodynamic, diuretic, kaliuretic, and natriuretic effects of AE. AE decreased rather than increased the RVR when IK were perfused with vasoconstrictors such as angiotensin II, norepinephrine, or vasopressin. The results demonstrate that AE acts directly on the kidney, eliciting powerful Ca-dependent hemodynamic and natriuretic responses. The natriuresis induced by AE can be accounted for, at least in part, by its renal hemodynamic effects rather than by the presence of a putative tubular natriuretic factor. The hypothesis is advanced that AE contains a substance(s) which behaves as a functional agonist/antagonist of endogenous vasoconstrictors with a preferential site of action on the efferent arterioles of the renal vasculature.

The Effects of Calcium and Calcium-Ionophores (X 537 a and a 23187) on Renin Release in the Isolated Perfused Rat Kidney

1978 ◽  
Vol 55 (s4) ◽  
pp. 163s-166s ◽  
Author(s):  
U. Schwertschlag ◽  
E. Hackenthal ◽  
R. Hackenthal ◽  
G. H. Rohs
Keyword(s):  
Indirect Effect ◽  
Indirect Effects ◽  
Vascular Tone ◽  
Rat Kidney ◽  
Renin Release ◽  
Direct And Indirect Effects ◽  
Calcium Depletion ◽  
A 23187 ◽  
Perfusate Flow ◽  
Perfused Rat Kidney

1. Calcium depletion from the medium of the isolated perfused kidney reduced renin release and renal perfusate flow. 2. Reintroduction of calcium increased renin release and perfusate flow. 3. The ionophore X 537 A (0·1–4 μmol/l) increased renin release both in the presence and absence of calcium in the medium. 4. The ionophore A 23187 (1–10 nmol/l) increased as well as decreased renin release. There was a positive correlation between direction of this effect and renal perfusate flow. 5. The results are compatible with the view that the effects of calcium and ionophores on renin release are the sum of direct and indirect effects of these agents, the predominant indirect effect being the modification of vascular tone.

scholarly journals Direct evidence that thromboxane mimetic U44069 preferentially constricts the afferent arteriole.

1997 ◽  
Vol 8 (1) ◽  
pp. 25-31
Author(s):  
K Hayashi ◽  
R Loutzenhiser ◽  
M Epstein
Keyword(s):  
Calcium Antagonist ◽  
Direct Evidence ◽  
Rat Kidney ◽  
Afferent Arteriole ◽  
Filtration Fraction ◽  
Perfused Rat Kidney ◽  
Txa2 Receptor ◽  
Txa2 Receptor Antagonist ◽  
Vasodilator Action ◽  
Hydronephrotic Kidney

The thromboxane A2 (TXA2) mimetic U44069 has been demonstrated to reduce the GFR and filtration fraction of the normal isolated perfused rat kidney markedly, suggesting a predominant constriction of preglomerular vessels. To assess this possibility directly, effects of U44069 on the renal microvessels of the isolated perfused hydronephrotic kidney were examined. At 10(-6) mol/L, U44069 elicited a 27 +/- 2% decrease in afferent arteriolar (AA) diameter (from 18.8 +/- 0.3 to 13.7 +/- 0.3 micron, P < 0.001). In contrast, efferent arteriolar (EA) diameter decreased by only 9 +/- 1% (from 16.4 +/- 0.5 to 15.0 +/- 0.5 micron, P < 0.001). These effects on both AA and EA were completely reversed by the TXA2 receptor antagonist SQ29548. The calcium antagonist diltiazem reversed U44069-induced AA constriction by 83 +/- 5%. The U44069-induced EA constriction was insensitive to the vasodilator action of diltiazem at concentrations from 10(-8) to 10(-6) mol/L, but at 10(-5) mol/L, diltiazem increased the EA diameter significantly, albeit modestly. Nifedipine also reversed the U44069-induced AA constriction (81 +/- 7%), but failed to inhibit the EA constriction at concentrations from 10(-9) to 10(-6) mol/L. These findings constitute the first direct evidence that a TXA2 agonist preferentially constricts the afferent arteriole. Furthermore, the ability of both the calcium antagonist and SQ29548 to reverse the renal microvascular actions of TXA2 agonists suggests a potential utility of these agents in ameliorating TXA2-induced renal hemodynamic abnormalities.

Anti-GBM antibody-induced proteinuria in isolated perfused rat kidney

1985 ◽  
Vol 249 (2) ◽  
pp. F241-F250 ◽  
Author(s):  
W. G. Couser ◽  
C. Darby ◽  
D. J. Salant ◽  
S. Adler ◽  
M. M. Stilmant ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Sodium Reabsorption ◽  
Glomerular Permeability ◽  
Flow Rates ◽  
Fluorescent Markers ◽  
Protein Excretion ◽  
Perfusate Flow ◽  
Perfused Rat Kidney ◽  
Fractional Clearance ◽  
And Control

The effect of anti-GBM antibody on protein excretion was studied in isolated rat kidneys perfused with 20 mg of sheep anti-rat GBM (experimental) or nonantibody sheep IgG (control). Six control kidneys excreted 176 +/- 31 micrograms/min of BSA initially, rising to 296 +/- 111 micrograms/min at 2 h. Fractional clearance of BSA rose from 0.51 to 1.70%. Eight experimental kidneys excreted 211 +/- 56 micrograms/min of BSA, increasing to 1,924 +/- 804 micrograms/min at 2 h. Fractional BSA clearance increased from 0.56 to 11.49%. After 60 min, BSA excretion in anti-GBM-perfused kidneys exceeded controls by a factor of 6.5-7.9 (P less than 0.05) and fractional BSA clearance exceeded controls by a factor of 5.8-7.1 (P less than 0.05). Studies with fluorescent markers indicated proteinuria to be of glomerular origin in antibody-perfused kidneys. There were no significant differences between anti-GBM-perfused and control kidneys in perfusion pressures, perfusate flow rates, urine flow rates, inulin clearance, or sodium reabsorption. Antibody to GBM can induce a marked increase in glomerular permeability to BSA and IgG without participation of other systemic humoral or cellular mediation systems.

Effect of bradykinin and kininogens in isolated rat kidney vasoconstricted by angiotensin II

1990 ◽  
Vol 258 (5) ◽  
pp. F1273-F1281 ◽  
Author(s):  
J. Gardes ◽  
T. Baussant ◽  
P. Corvol ◽  
J. Menard ◽  
F. Alhenc-Gelas
Keyword(s):  
Molecular Weight ◽  
Angiotensin Ii ◽  
High Molecular Weight ◽  
Rat Kidney ◽  
Renin Secretion ◽  
Ang Ii ◽  
Urinary Kallikrein ◽  
High Molecular Weight Kininogen ◽  
Perfusate Flow ◽  
Isolated Rat

The hemodynamic and endocrine effects of bradykinin and kininogens were investigated using a closed-circuit isolated rat kidney perfused with angiotensin II (ANG II). ANG II induced vasoconstriction, stimulation of urinary kallikrein release, and inhibition of renin secretion. Bradykinin markedly increased renal perfusate flow (RPF) and produced a slight but significant diuresis and natriuresis. The inhibitory effect of ANG II on renin secretion was delayed. Urinary kallikrein secretion was unchanged. The effect of bradykinin was suppressed by the competitive kinin antagonist [DArg,Hyp3,Thi5,8,DPhe7]bradykinin. Kallikrein-sensitive rat high-molecular-weight kininogen produced a progressive rise in renal perfusate flow. Exocrine function and renin and kallikrein secretions were unchanged. Immunoreactive kinins, identified as bradykinin by high-pressure liquid chromatography, were liberated into the perfusate. Perfusate immunoreactive high-molecular-weight kininogen decreased in parallel as a result of consumption. The kalikrein-resistant T-kininogen was not hydrolyzed to release a kinin, had no effect on renal function, and its concentration in the perfusate remained constant. These results suggest that kinin can be produced in the renal circulation from kallikrein-sensitive circulating kininogens and can antagonize the vasoconstrictor effect of ANG II and alter renal hemodynamics. They provide evidence that the kallikrein-kinin system can participate with the renin-angiotensin system in the control of renal blood flow.

Physiological evaluation of the isolated perfused rat kidney

1980 ◽  
Vol 238 (2) ◽  
pp. F71-F78 ◽  
Author(s):  
T. Maack
Keyword(s):  
Rat Kidney ◽  
Critical Evaluation ◽  
Proximal Convoluted Tubule ◽  
Urinary Concentration ◽  
Isolated Perfused Rat Kidney ◽  
Low Viscosity ◽  
Metabolic Functions ◽  
Perfusate Flow ◽  
Perfused Rat Kidney ◽  
Single Nephron

A critical evaluation of the functional properties of the isolated perfused rat kidney is necessary to assess the usefulness of the preparation for renal function studies. Clearance and micropuncture experiments in isolated perfused rat kidneys perfused with a plasmalike medium containing 7.5 g/100 ml albumin, glucose, and amino acids show that proximal convoluted tubule functions are well preserved. Proximal convoluted tubule reabsorption of organic substances, electrolytes, and fluid is near normal, the latter being directly related to the peritubular oncotic pressure. Superficial single nephron glomular filtration rate and glomerular permselectivity are also preserved. However, abnormalities in renal hemodynamics, urinary concentration-dilution, and excretion of fluid and electrolytes persist even in the best preparations. High renal perfusate flow, due mainly to the low viscosity of the perfusate, and altered distal nephron functions explain at least in part these abnormalities. Therefore, the isolated perfused rat kidney is a useful preparation to particularly study glomerular and proximal convoluted tubule functions. Recent development of a nonfiltering isolated perfused rat kidney model, with preserved renal perfusate flow and cellular integrity, also permits the study of transport and metabolic functions of proximal tubular cells independently of luminal events.

Effects of adenosine receptor antagonists on the responses to contrast media in the isolated rat kidney

2000 ◽  
Vol 98 (3) ◽  
pp. 303-311 ◽  
Author(s):  
Simon D. OLDROYD ◽  
Lu FANG ◽  
John L. HAYLOR ◽  
Michael S. YATES ◽  
A. Meguid EL NAHAS ◽  
...  
Keyword(s):  
Contrast Media ◽  
Receptor Antagonist ◽  
Mesangial Cell ◽  
Rat Kidney ◽  
Perfusate Flow ◽  
Perfused Rat Kidney ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Renal Vascular

Contrast media can induce both a decrease in renal blood flow and a reduction in glomerular filtration rate (GFR) when administered to both experimental animals and humans. In the present study we have examined the role of adenosine in mediating these effects using the isolated perfused rat kidney. Kidneys were perfused with a 6.7%-(w/v)-albumin-based perfusate supplemented with glucose and amino acids (n = 6 per group). They were exposed to diatrizoate [20 mg of iodine (mgI)/ml; osmolality 1650 mOsm/kg of water] or iotrolan (20 mgI/ml; osmolality 320 mOsm/kg of water) in the presence or absence of theophylline (10.8 µg/ml), or to diatrizoate in the presence or absence of a specific adenosine A1 receptor antagonist (KW-3902; 2 µg/ml) or a specific A2 receptor antagonist (KF17837; 6 µg/ml). Diatrizoate (n = 6) produced a fall in GFR from 0.65±0.04 to 0.42±0.03 ml·min-1·g-1 (P < 0.05); renal perfusate flow (RPF) also declined, from 36.5±3.8 to 22.0±3.2 ml·min-1·g-1 (P < 0.05). Iotrolan (n = 6) produced a fall in GFR from 0.64±0.02 to 0.48±0.04 ml·min-1·g-1 (P < 0.05) and in RPF from 33.3±3.8 to 24.0±3.0 ml·min-1·g-1 (P < 0.05). Theophylline (10.8 µg/ml) prevented the fall in GFR caused by either diatrizoate (baseline, 0.63±0.05 ml·min-1·g-1; diatrizoate+theophylline, 0.60±0.04 ml·min-1·g-1) or iotrolan (basline, 0.64±0.04 ml·min-1·g-1; iotrolan+theophylline, 0.67±0.05 ml·min-1·g-1), but did not affect the decreases in RPF caused by either agent. KW-3902 (2 µg/ml) also prevented the fall in GFR produced by diatrizoate (baseline, 0.66±0.05 ml·min-1·g-1; diatrizoate+KW-3902, 0.61±0.05 ml·min-1·g-1), while the fall in RPF remained unaffected. KF17837 (6 µg/ml) had no effect on the decreases in either GFR or RPF induced by diatrizoate (n = 6 per group). The results suggest a role for adenosine acting at the A1 receptor in mediating the decrease in GFR induced by contrast media. This effect is independent of a change in renal vascular resistance, and possibly secondary to mesangial cell contraction causing a decrease in the ultrafiltration coefficient.

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