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.

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.

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.

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

The Renal Kallikrein-Kinin System in Renoparenchymal Hypertension

1989 ◽  
pp. 127-132 ◽  
Author(s):  
Toshiaki Ando ◽  
Kazuaki Shimamoto ◽  
Nobuyuki Ura ◽  
Toyoharu Yokoyama ◽  
Shuzaburo Fukuyama ◽  
...  
Keyword(s):  
Kinin System ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System

scholarly journals Bradykinin acutely inhibits activity of the epithelial Na+ channel in mammalian aldosterone-sensitive distal nephron

2011 ◽  
Vol 300 (5) ◽  
pp. F1105-F1115 ◽  
Author(s):  
Oleg Zaika ◽  
Mykola Mamenko ◽  
Roger G. O'Neil ◽  
Oleh Pochynyuk
Keyword(s):  
Critical Role ◽  
Na Channel ◽  
Open Probability ◽  
Kinin System ◽  
Renal Kallikrein ◽  
Subsequent Activation ◽  
Patch Clamp Electrophysiology ◽  
B2 Receptors ◽  
Renal Tubular ◽  
Kallikrein Kinin System

Activation of the renal kallikrein-kinin system results in natriuresis and diuresis, suggesting its possible role in renal tubular sodium transport regulation. Here, we used patch-clamp electrophysiology to directly assess the effects of bradykinin (BK) on the epithelial Na+ channel (ENaC) activity in freshly isolated split-opened murine aldosterone-sensitive distal nephrons (ASDNs). BK acutely inhibits ENaC activity by reducing channel open probability ( Po) in a dose-dependent and reversible manner. Inhibition of B2 receptors with icatibant (HOE-140) abolished BK actions on ENaC. In contrast, activation of B1 receptors with the selective agonist Lys-des-Arg9-BK failed to reproduce BK actions on ENaC. This is consistent with B2 receptors playing a critical role in mediating BK signaling to ENaC. BK has little effect on ENaC Po when Gq/11 was inhibited with Gp antagonist 2A. Moreover, inhibition of phospholipase C (PLC) with U73122, but not saturation of cellular cAMP levels with the membrane-permeable nonhydrolysable cAMP analog 8-cpt-cAMP, prevents BK actions on ENaC activity. This argues that BK stimulates B2 receptors with subsequent activation of Gq/11-PLC signaling cascade to acutely inhibit ENaC activity. Activation of BK signaling acutely depletes apical PI( 4 , 5 )P2 levels. However, inhibition of Ca2+ pump SERCA of the endoplasmic reticulum with thapsigargin does not prevent BK signaling to ENaC. Furthermore, caffeine, while producing a similar rise in [Ca2+]i as in response to BK stimulation, fails to recapitulate BK actions on ENaC. Therefore, we concluded that BK acutely inhibits ENaC Po in mammalian ASDN via stimulation of B2 receptors and following depletion of PI( 4 , 5 )P2, but not increases in [Ca2+]i.

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