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.

scholarly journals Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring

2010 ◽  
Vol 298 (5) ◽  
pp. R1421-R1427 ◽  
Author(s):  
Norma B. Ojeda ◽  
Thomas P. Royals ◽  
Joshua T. Black ◽  
John Henry Dasinger ◽  
Jeremy M. Johnson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Ang Ii ◽  
Enhanced Sensitivity ◽  
And Control

Placental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growth-restricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg·kg−1·day−1) for 1 wk. Baseline blood pressures were similar between growth-restricted (112 ± 3 mmHg) and control (110 ± 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng·kg−1·min−1 for 30 min) was observed in growth-restricted (160 ± 2 mmHg) vs. control (136 ± 2 mmHg; P < 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growth-restricted (130 ± 2 mmHg) rats with no significant effect on blood pressure in controls (130 ± 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 μg/min) in control (184 ± 5 mmHg) and growth-restricted (184 ± 8 mmHg) rats, suggesting the enhanced pressor response in growth-restricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR.

Effect of ANG II receptor antagonist on albuminuria and renal function in passive Heymann nephritis

1992 ◽  
Vol 263 (2) ◽  
pp. F311-F318
Author(s):  
F. N. Hutchinson ◽  
S. K. Webster
Keyword(s):  
Blood Pressure ◽  
Receptor Antagonist ◽  
Enzyme Inhibitor ◽  
Pressor Response ◽  
Plasma Renin ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Heymann Nephritis

Angiotensin-converting enzyme inhibitors reduce albuminuria in nephrotic subjects, but the hormonal mechanism of this effect is not known. To determine whether specific inhibition of angiotensin (ANG) II activity would decrease albuminuria as occurs after converting enzyme inhibition, rats with passive Heymann nephritis received enalapril or the ANG II receptor antagonist losartan (6 mg.kg-1.day-1) for 4 days. Enalapril reduced both albuminuria (from 583 +/- 53 to 286 +/- 55 mg/day, P less than 0.001) and the fractional clearance of albumin (FCAlb) each day after starting treatment but did not affect glomerular filtration rate (GFR). Losartan reduced albuminuria significantly only after 4 days of treatment, but this value was not different from controls. GFR significantly increased with losartan (from 1.24 +/- 0.09 to 1.73 +/- 0.21 ml/min, P less than 0.05) so that FCAlb was reduced (from 0.0134 +/- 0.0027 to 0.0080 +/- 0.0018, P less than 0.05). Blood pressure decreased only in the enalapril group. Although plasma renin activity increased and the pressor response to ANG I was inhibited by both enalapril and losartan, suggesting effective peripheral blockade of ANG II activity, a third group of nephrotic rats was treated with losartan (18 mg.kg-1.day-1) to ensure that adequate ANG II blockade was achieved. Blood pressure decreased 10 mmHg, GFR increased from 1.35 +/- 0.14 to 1.79 +/- 0.12 ml/min (P less than 0.01), but albuminuria and FCAlb did not change. Urinary total kallikrein excretion was increased only in nephrotic rats treated with enalapril. Although both enalapril and losartan reduce ANG II activity, only the converting enzyme inhibitor reduces albuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue kallikrein deficiency and renovascular hypertension in the mouse

2009 ◽  
Vol 296 (5) ◽  
pp. R1385-R1391 ◽  
Author(s):  
Violaine Griol-Charhbili ◽  
Laurent Sabbah ◽  
Juliana Colucci ◽  
Marie-Pascale Vincent ◽  
Véronique Baudrie ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Tissue Kallikrein ◽  
Kinin System ◽  
Kidney Blood Flow ◽  
Kallikrein Kinin System

The kallikrein kinin system (KKS) is involved in arterial and renal functions. It may have an antihypertensive effect in both essential and secondary forms of hypertension. The role of the KKS in the development of two-kidneys, one-clip (2K1C) hypertension, a high-renin model, was investigated in mice rendered deficient in tissue kallikrein (TK) and kinins by TK gene inactivation (TK−/−) and in their wild-type littermates (TK+/+). Four weeks after clipping the renal artery, blood flow was reduced in the clipped kidney (2K1C-TK+/+: −90%, 2K1C-TK−/−: −93% vs. sham-operated mice), and the kidney mass had also decreased (2K1C-TK+/+: −65%, 2K1C-TK−/−: −66%), whereas in the unclipped kidney, blood flow (2K1C-TK+/+: +19%, 2K1C-TK−/−: +17%) and kidney mass (2K1C-TK+/+: +32%, 2K1C-TK−/−: +30%) had both increased. The plasma renin concentration (2K1C-TK+/+: +78%, 2K1C-TK−/−: +65%) and renal renin content of the clipped kidney (2K1C-TK+/+: +58%, 2K1C-TK−/−: +65%) had increased significantly. There was no difference for these parameters between 2K1C-TK+/+ and 2K1C-TK−/− mice. Blood pressure monitored by telemetry and by plethysmography, rose immediately after clipping in both genotypes, and reached similar levels (2K1C-TK+/+: +24%, 2K1C-TK−/−: +21%). 2K1C-TK+/+ and 2K1C-TK−/− mice developed similar concentric left ventricular hypertrophy (+24% and +17%, respectively) with normal cardiac function. These findings suggest that in the context of chronic unilateral reduction in renal blood flow, TK and kinins do not influence the trophicity of kidneys, the synthesis and secretion of renin, blood pressure increase, and cardiac remodeling due to renin angiotensin system activation.

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.

Potassium supplement upregulates the expression of renal kallikrein and bradykinin B2receptor in SHR

1999 ◽  
Vol 276 (3) ◽  
pp. F476-F484 ◽  
Author(s):  
Lan Jin ◽  
Lee Chao ◽  
Julie Chao
Keyword(s):  
Blood Pressure ◽  
Tissue Kallikrein ◽  
Mrna Levels ◽  
High Potassium ◽  
Kinin System ◽  
Glomerular Lesion ◽  
Potassium Supplement ◽  
Potassium Intake ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System

High potassium intake is known to attenuate hypertension, glomerular lesion, ischemic damage, and stroke-associated death. Our recent studies showed that expression of recombinant kallikrein by somatic gene delivery reduced high blood pressure, cardiac hypertrophy, and renal injury in hypertensive animal models. The aim of this study is to explore the potential role of the tissue kallikrein-kinin system in blood pressure reduction and renal protection in spontaneously hypertensive rats (SHR) on a high-potassium diet. Young SHR were given drinking water with or without 1% potassium chloride for 6 wk. Systolic blood pressure was significantly reduced beginning at 1 wk, and the effect lasted for 6 wk in the potassium-supplemented group compared with that in the control group. Potassium supplement induced 70 and 40% increases in urinary kallikrein levels and renal bradykinin B2 receptor density, respectively ( P < 0.05), but did not change serum kininogen levels. Similarly, Northern blot analysis showed that renal kallikrein mRNA levels increased 2.7-fold, whereas hepatic kininogen mRNA levels remained unchanged in rats with high potassium intake. No difference was observed in β-actin mRNA levels in the kidney or liver of either group. Competitive RT-PCR showed a 1.7-fold increase in renal bradykinin B2 receptor mRNA levels in rats with high potassium intake. Potassium supplement significantly increased water intake, urine excretion, urinary kinin, cAMP, and cGMP levels. This study suggests that upregulation of the tissue kallikrein-kinin system may be attributed, in part, to blood pressure-lowering and diuretic effects of high potassium intake.

Characterization of the renin-angiotensin system in the turtle Pseudemys scripta

1984 ◽  
Vol 247 (1) ◽  
pp. R15-R23 ◽  
Author(s):  
M. D. Cipolle ◽  
J. E. Zehr
Keyword(s):  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Ang Ii ◽  
Freshwater Turtles ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Fourfold Increase ◽  
Inactive Form ◽  
Pseudemys Scripta

Studies were conducted in freshwater turtles Pseudemys scripta to define some characteristics of the renin-angiotensin system in this reptile. Dialyzed acid-treated kidney extract (1 g tissue per ml water) produced a prolonged pressor response in unanesthetized turtles, which was eliminated by boiling the extract or by pretreating the turtle with [Sar1, Ile8]angiotensin II. A rat pressor assay was employed because turtle angiotensin (ANG) was bound poorly by the anti-[Asp1, Ile5, His9]ANG I used in our radioimmunoassay. Kidney extract incubated with homologous plasma (pH 5.5 and 25 degrees C) produced a time-dependent pressor response in rats. The pressor activity of the product was eliminated by dialysis or by pretreating the rats with [Sar1, Ile8]ANG II. The pressor response in anesthetized turtles to ANG I was significantly reduced by captopril, whereas the ANG II response remained unchanged, thus demonstrating the presence of ANG-converting enzyme activity in these animals. We determined the velocity of turtle ANG formation at various dilutions of enzyme (kidney extract) or substrate (plasma). Turtle kidney extract incubated with homologous plasma displayed typical Michaelis-Menten kinetics. Finally we conducted experiments to determine whether a portion of turtle plasma renin exists in an inactive form. Trypsinization caused a slight increase in plasma renin activity (PRA), whereas acidification to pH 3.3 yielded a fourfold increase in PRA.

Interference of Converting Enzyme Inhibitors with the Kallikrein-Kinin System

1983 ◽  
Vol 5 (7-8) ◽  
pp. 1277-1285 ◽  
Author(s):  
Oscar A. Carretero ◽  
Torill Berg ørstavik ◽  
Sara F. Rabito ◽  
A. Guillermo Scicli
Keyword(s):  
Enzyme Inhibitors ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Kinin System ◽  
Kallikrein Kinin System
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