Steroid induced changes of the renal kallikrein-kinin system in rats

1984 ◽  
Vol 107 (1) ◽  
pp. 131-140 ◽  
Author(s):  
G. Bönner ◽  
R. Autenrieth ◽  
M. Marin-Grez ◽  
G. Speck ◽  
F. Gross
Keyword(s):  
Urinary Excretion ◽  
Time Course ◽  
Urine Volume ◽  
Renin Angiotensin System ◽  
Sprague Dawley ◽  
Kinin System ◽  
Salt Loading ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System ◽  
Kallikrein Activity

Abstract. In male Sprague-Dawley rats the influence of salt loading (1% NaCl), deoxycorticosterone acetate (2 × 15 mg/kg/day resp. 250 mg/kg sc), corticosterone (2 × 20 mg/kg/day sc) and adrenocorticosterone (0.5 mg/kg/day tetracosactid sc) on the activity of renal kallikrein and renal renin activity was investigated. Salt loading lowered renal kallikrein activity, deoxycorticosterone stimulated its activity and in combination they had no effect on renal kallikrein activity. The time course of kallikrein stimulation by deoxycorticosterone showed no relationship to the escape phenomenon of the kidney from the sodium retaining effect of the mineralocorticoid hormone. Reduction of endogenous mineralcorticoid hormones by adrenalectomy caused a marked reduction of urinary and renal kallikrein activity. Corticosterone suppressed the activity of the renal kallikrein-kinin system at the same time as the reduction in urinary aldosterone excretion. Adrenocorticotrophin caused the same decrease in the activity of renal kallikrein as corticosterone. Urinary aldosterone excretion, however, was significantly stimulated. Thus, the known positive correlation between kallikrein and aldosterone was missing. In all experiments the urinary excretion of kallikrein correlated highly with the kallikrein activity measured in renal cortical tissue. However, no correlation was found between kallikrein and urine volume or urinary excretion of sodium and potassium. In our experiments no relationship between the activity of the renin-angiotensin system and that of the renal kallikrein-kinin system was observed. Furthermore, no clear relationship was found between systemic blood pressure and the activity of the renal kallikrein-kinin system.

Effects of Frusemide on the Renal Kallikrein–Kinin System of the Rat

1982 ◽  
Vol 63 (5) ◽  
pp. 447-453 ◽  
Author(s):  
G. Bönner ◽  
D. Beck ◽  
M. Deeg ◽  
M. Marin-Grez ◽  
F. Gross
Keyword(s):  
Renal Cortex ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Biphasic Response ◽  
Kinin System ◽  
Forced Diuresis ◽  
Renal Kallikrein ◽  
Male Wistar Rats ◽  
Kallikrein Kinin System ◽  
Kallikrein Activity

1. In male Wistar rats, three doses of frusemide (0·5, 5·0 and 50·0 mg/kg) were injected subcutaneously. A dose-related increase in urine flow and natriuresis occurred, whereas there was a biphasic response in kallikrein excretion with an initial, dose-related transient increase and a secondary reduction. When the urine losses were replaced by the infusion of 0·9% NaCl solution, the biphasic response of urinary kallikrein excretion was maintained. 2. In all experiments, urinary excretion of kallikrein correlated with the excretion of potassium. Frusemide enhanced the excretion of kinins, which correlated with the urine volume and the natriuresis, but not with kallikrein excretion. 3. In contrast to the initially increased excretion of kallikrein, kallikrein activity in the renal cortex remained unchanged or was even reduced. Kininogen content of the perfused tissue of the renal cortex did not vary throughout the experiment, but decreased markedly in the non-perfused tissue of the cortex 30 min after the injection of frusemide. 4. It is concluded that forced diuresis induced by frusemide causes a ‘wash out’ of renal kallikrein in urine, probably not indicating the true changes in the activity of the renal kallikrein-kinin system within the kidney. Kinin excretion in urine was not correlated with kallikrein excretion but with changes in diuresis. Thus it might be suggested that the renal kallikrein-kinin system could be involved by kinins in the regulation of renal water and sodium excretion as well as of renal plasma flow.

Influence of sodium balance on urinary excretion of immunoreactive kinins in rats

1988 ◽  
Vol 254 (4) ◽  
pp. F484-F491 ◽  
Author(s):  
J. Barabe ◽  
D. Huberdeau ◽  
A. Bernoussi
Keyword(s):  
Regression Analysis ◽  
Urinary Excretion ◽  
Sodium Balance ◽  
Small Decrease ◽  
Sodium Depletion ◽  
Urinary Volume ◽  
Kinin System ◽  
Positive Correlation ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System

Antibodies against bradykinin (BK) and its metabolites, namely des-Arg9-BK and des-Phe8,Arg9-BK were raised in rabbits, and specific radioimmunoassays (RIA) for these peptides were developed. Specificity studies showed that each RIA was specific for its antigen, since the cross-reactivities of various kinin-related peptides were less than 1.5%. The lowest concentration of peptide that could be measured in these assays was approximately 60 pg/ml. The antibodies were used to measure concentrations of BK and its metabolites in urine and kidneys of rats maintained on different sodium balance for 5 wk. The results showed that normal rats excrete low quantities of BK (63.78 +/- 2.98 ng/day, 88 determinations). The urinary excretion of des-Arg9-BK averaged 77.69 +/- 5.53 ng/day, whereas the amount of des-Phe8,Arg9-BK is equal to 7.13 +/- 0.42 ng/day. Sodium loading brings about a small decrease in the concentration of BK (45.57 +/- 2.36 ng/day, 76 determinations), whereas sodium depletion significantly increased the excretion of BK (94.23 +/- 5.50, 102 determinations, P less than 0.01) accompanied by no modification of the excretion of metabolites. Regression analysis of the results showed a positive correlation between urinary volume and BK in control and sodium-loaded animals and urinary BK and sodium in the sodium-loaded group. In kidney homogenates, sodium depletion increased not only the concentration of BK (10-fold) but also that of des-Arg9-BK and des-Phe8,Arg9-BK by a factor of four and two, respectively, when compared with normal and sodium-loaded animals. These results support the hypothesis that the renal kallikrein-kinin system may be regulated by corticosteroids.

Effects of modulation of renal kallikrein-kinin system in the nephrotic syndrome

1990 ◽  
Vol 258 (5) ◽  
pp. F1237-F1244
Author(s):  
F. N. Hutchison ◽  
V. I. Martin
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitors ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Ang Ii ◽  
Converting Enzyme Inhibitors ◽  
Kinin System ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System

Albuminuria (UAlbV) can be reduced by converting-enzyme inhibitors (CEI), but the hormonal mechanism responsible for this effect has not previously been defined. Since CEI increase kinin activity as well as reduce angiotensin II (ANG II) activity, experiments were performed to determine the effect of isolated alterations in kinin and ANG II metabolism on UAlbV in rats with passive Heymann pephritis. Phosphoramidon was used to potentiate kinin activity without altering ANG II synthesis. Aprotinin was utilized in combination with the CEI, enalapril, to prevent the increase in kinin activity caused by CEI. UAlbV and the fractional renal clearance of albumin (FCAlb) decreased significantly after either phosphoramidon or enalapril, although only enalapril reduced blood pressure. Glomerular filtration rate (GFR) was not affected by either drug. Phosphoramidon did not affect plasma renin activity (PRA) or the pressor response to angiotensin I (ANG I), indicating that ANG II synthesis was not altered. Aprotinin prevented the reduction in UAlbV and FCAlb produced by CEI but not the hypotension, elevated PRA, or ANG I pressor blockade produced by CEI. Aprotinin alone had no effect on UAlbV, GFR, PRA, or blood pressure. UAlbV can be reduced by increasing kinin activity by a mechanism that is not dependent on suppression of ANG II activity or reduction in GFR or blood pressure. CEI may reduce proteinuria as a result of their action on the kallikrein-kinin system rather than on the renin-angiotensin system.

Renin-angiotensin system modulates renal bradykinin production

1996 ◽  
Vol 271 (4) ◽  
pp. R1090-R1095 ◽  
Author(s):  
H. M. Siragy ◽  
A. A. Jaffa ◽  
H. S. Margolius ◽  
R. M. Carey
Keyword(s):  
Renal Plasma Flow ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Sodium Depletion ◽  
Kinin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System ◽  
Cgmp Formation

Previous studies have shown that sodium depletion is associated with an increase in renal kallikrein-kinin system activity. This system may play an important role in counterbalancing the renal effects of the renin-angiotensin system. In this study, we examined whether the renal renin-angiotensin system participates in the regulation of renal bradykinin (BK) levels during sodium depletion. We measured changes in renal excretory and hemodynamic function, renal interstitial fluid (RIF) BK, and RIF and urinary guanosine 3',5'-cyclic monophosphate (cGMP) and prostaglandin E2 (PGE2) in conscious uninephrectomized dogs (n = 5) in sodium metabolic balance (10 meq/day) in response to intrarenal arterial administration of the renin inhibitor ACRIP (0.2 microgram.kg-1.min-1) or angiotensin II AT1-receptor blocker losartan (100 ng.kg-1.min-1). ACRIP and losartan increased urine flow rate from 0.75 +/- 0.06 to 1.6 +/- 0.03 and 1.5 +/- 0.05 ml/min, respectively (each P < 0.001), and urine sodium excretion from 5.4 +/- 0.7 to 18.3 +/- 1.3 and 15.9 +/- 1.2 meq/min, respectively (each P < 0.001). Glomerular filtration rate and renal plasma flow increased only during losartan administration (P < 0.05). ACRIP decreased RIF BK by 48%, from 33.1 +/- 3.8 to 17.4 +/- 4.1 pg/min (P < 0.01). ACRIP decreased RIF cGMP by 38%, from 0.69 +/- 0.08 to 0.43 +/- 0.1 pmol/min (P < 0.01); urinary cGMP by 16%, from 0.63 +/- 0.05 to 0.53 +/- 0.02 pmol/min (P < 0.05); and RIF PGE2 by 46%, from 10.5 +/- 1.1 to 5.7 +/- 1.1 pg/min (P < 0.01). Urinary PGE2 was unchanged by ACRIP. Losartan decreased RIF PGE2 by 71%, from 10.8 +/- 0.6 to 3.1 +/- 0.6 pg/min (P < 0.01) but failed to change RIF BK, RIF cGMP, urinary cGMP, or urinary PGE2. These data suggest that the renin-angiotensin system tonically stimulates renal BK production and cGMP formation via a non-AT1 angiotensin receptor and renal PGE2 production via the AT1 receptor.

Spatial and temporal expression of kallikrein and its mRNA during nephron maturation

1992 ◽  
Vol 262 (5) ◽  
pp. F705-F711 ◽  
Author(s):  
S. S. el-Dahr ◽  
J. Chao
Keyword(s):  
Adult Life ◽  
Sprague Dawley ◽  
Outer Cortex ◽  
Developmentally Regulated ◽  
Mrna Accumulation ◽  
Kinin System ◽  
Fourfold Increase ◽  
Renal Kallikrein ◽  
Distal Tubules ◽  
Kallikrein Kinin System

To determine the relationships between nephron maturation and the ontogeny of intrarenal kallikrein, the expression and distribution of kallikrein and its mRNA were examined in fetal, neonatal, and adult Sprague-Dawley rats. Kallikrein-like immunoreactivity was first expressed 1 day before birth in the upper limb of S-shaped bodies. Immediately after birth, kallikrein immunostaining was present along the apical membranes of inner cortical distal tubules, whereas subcapsular less mature comma-shaped vesicles did not express kallikrein. After completion of nephrogenesis, kallikrein was also seen in the distal and connecting tubules of the outer cortex. In situ hybridization localized the kallikrein message in the distal tubules of inner cortical nephrons in newborns and outer cortex in adults. The transition from newborn to adult life was associated with six- and fourfold increase in renal kallikrein content and mRNA accumulation, respectively. We conclude that immature distal tubules have the transcriptional and translational capacity to express the kallikrein gene and protein and that the renal kallikrein gene is developmentally regulated. The spatial and temporal changes in intrarenal kallikrein expression during ontogeny are consistent with the hypothesis that the kallikrein-kinin system plays a role in the maturation of renal functions.

scholarly journals Functional, biochemical, and molecular investigations of renal kallikrein-kinin system in diabetic rats

1999 ◽  
Vol 277 (6) ◽  
pp. H2333-H2340 ◽  
Author(s):  
C. Tschöpe ◽  
A. Reinecke ◽  
U. Seidl ◽  
M. Yu ◽  
V. Gavriluk ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Single Injection ◽  
Neutral Endopeptidase ◽  
Diabetic Rats ◽  
Kinin System ◽  
Fold Reduction ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System ◽  
Kallikrein Activity ◽  
Renal Expression

A reduction of renal kallikrein has been found in non-insulin-treated diabetic individuals, suggesting that an impaired renal kallikrein-kinin system (KKS) contributes to the development of diabetic nephropathy. We analyzed relevant components of the renal KKS in non-insulin-treated streptozotocin (STZ)-induced diabetic rats. Twelve weeks after a single injection of STZ, rats were normotensive and displayed hyperglycemia, polyuria, proteinuria, and reduced glomerular filtration rate. Blood bradykinin (BK) levels and prekallikrein activity were significantly increased compared with controls. Renal kallikrein activity was reduced by 70%, whereas urinary BK levels were increased up to threefold. Renal kininases were decreased as indicated by a 3-fold reduction in renal angiotensin-converting enzyme activity and a 1.8-fold reduction in renal expression of neutral endopeptidase 24.11. Renal cortical expression of kininogen and B2receptors was enhanced to 1.4 and 1.8-fold, respectively. Our data suggest that increased urinary BK levels found in severely hyperglycemic STZ-diabetic rats are related to increased filtration of components of the plasma KKS and/or renal kininogen synthesis in combination with decreased renal kinin-degrading activity. Thus, despite reduced renal kallikrein synthesis, renal KKS is activated in the advanced stage of diabetic nephropathy.

scholarly journals Postnatal maturation of the Kallikrein-kinin system in the rat kidney: from enzyme activity to receptor gene expression.

1996 ◽  
Vol 7 (1) ◽  
pp. 81-89 ◽  
Author(s):  
J L Bascands ◽  
M E Marin Castaño ◽  
G Bompart ◽  
C Pecher ◽  
M Gaucher ◽  
...  
Keyword(s):  
Binding Sites ◽  
Rat Kidney ◽  
Kinin System ◽  
Postnatal Maturation ◽  
Beta Actin ◽  
Age Related ◽  
Renal Kallikrein ◽  
Actin Mrna ◽  
Kallikrein Kinin System ◽  
Kallikrein Activity

During the course of aging, the balance between intrarenal hormones is disturbed. These age-related changes are well documented for the vasoconstrictor renin-angiotensin system, but comparable information on the renal kallikrein-kinin system is not yet available. The status of the kallikrein-kinin system was assessed by (1) kallikrein activity, measured by RIA; (2) maximum binding site density (Bmax) and affinity (Kd) of nonapeptide bradykinin (BK)-2 receptor, estimated by binding assays; (3) expression of BK2-receptor receptor mRNA, detected by reverse transcription-polymerase chain reaction (RT-PCR) using specific BK2-oligonucleotide primers. These parameters were determinated on renal glomeruli of 3-, 5-, 8-, 12- and 38-wk-old normotensive rats. Kallikrein activity increased from 3.2 to 7.7 ng BK/min per mg protein. The density of BK2 binding sites also rose from 12 to 40 femtomoles/mg protein with no difference in affinity. There was no change in specificity, which remained that expected of a BK2 receptor. The increase in the density of BK2 binding sites was associated with an augmented mRNA expression, whereas beta-actin mRNA used as a control remained unchanged. The ratio of BK2 mRNA to beta-actin mRNA indicated maximum steady expression after 8 wk of age. The data provide evidence that the renal kallikrein-kinin system develops postnatally.

The renal kallikrein-kinin system

1980 ◽  
Vol 238 (4) ◽  
pp. F247-F255 ◽  
Author(s):  
O. A. Carretero ◽  
A. G. Scicli
Keyword(s):  
Kinin System ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System

scholarly journals ALDOSTERONE--A POTENT STIMULATOR OF THE RENAL KALLIKREIN-KININ SYSTEM DURING FETAL LIFE

1984 ◽  
Vol 18 ◽  
pp. 368A-368A
Author(s):  
Jean E Robillard ◽  
Kenneth T Nakamura ◽  
Oliva McWeeny ◽  
Sindy Wear ◽  
William Lawton
Keyword(s):  
Fetal Life ◽  
Kinin System ◽  
Potent Stimulator ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System
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