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.

Effect of cyclosporin A on the expression of tissue kallikrein, kininogen, and bradykinin receptor in rat

1997 ◽  
Vol 273 (5) ◽  
pp. F783-F789
Author(s):  
Cindy Wang ◽  
Philbert Ford ◽  
Caroline Chao ◽  
Lee Chao ◽  
Julie Chao
Keyword(s):  
Blood Pressure ◽  
Cyclosporin A ◽  
Chronic Administration ◽  
Tissue Kallikrein ◽  
Mrna Levels ◽  
Kinin System ◽  
Bradykinin Receptor ◽  
System Components ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System

The tissue kallikrein-kinin system is involved in vasodilation and blood pressure regulation. In the present study, we investigated the effects of chronic cyclosporin A (CsA) administration on blood pressure and the expression of tissue kallikrein, kininogen, and bradykinin receptor in normotensive Wistar rats. Chronic administration of CsA significantly increased systolic blood pressure compared with control rats ( n = 6, P < 0.01), although body weight was significantly lower than control rats ( n = 6, P < 0.01). The development of hypertension was accompanied by the altered expression of kallikrein-kinin system components. Immunoreactive renal kallikrein and urinary excretion of tissue kallikrein levels were increased by chronic administration of CsA ( n = 5 or 6, P < 0.05). Levels of N-tosyl-l-phenylalanine chloromethyl ketone-trypsin and kallikrein-releasable kininogens in sera increased in response to chronic CsA treatment ( n = 5 or 6, P < 0.05). Chronic CsA treatment significantly increased renal kallikrein, bradykinin B2 receptor, and hepatic kininogen mRNA levels. The increased levels of tissue kallikrein-kinin system components were accompanied by significant increases in 24-h urine excretion and water intake after chronic CsA treatment ( n = 5, P < 0.05). These results suggest that enhanced activity of the tissue kallikrein-kinin system may compensate for the CsA-induced vasoconstriction and hypertension.

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.

Developmentally regulated kallikrein enzymatic activity and gene transcription rate in maturing rat kidneys

1993 ◽  
Vol 265 (1) ◽  
pp. F146-F150 ◽  
Author(s):  
S. S. el-Dahr ◽  
I. Yosipiv
Keyword(s):  
Gene Transcription ◽  
Transcription Rate ◽  
Tissue Kallikrein ◽  
Mrna Levels ◽  
Female Rat ◽  
Kinin System ◽  
Transcription Analysis ◽  
Renal Kallikrein ◽  
Kallikrein Activity ◽  
Rat Kidneys

Kinins are paracrine vasoactive and growth-modulating peptides. Kidney maturation is accompanied by enhanced accumulation of the mRNA encoding tissue (renal) kallikrein, a serine protease, and a key component of the kallikrein-kinin system. To further delineate the developmental regulation of renal kallikrein, we measured tissue kallikrein activity and gene transcription rate during the latter stages of metanephrogenesis. Active tissue kallikrein was measured in renal homogenates by the amidolytic assay using the fluorogenic substrate D-Val-Leu-Arg-7-amino-4-methylcoumarin (D-VLR-AMC) in the presence or absence of soybean trypsin inhibitor (SBTI). Kallikrein activity was detectable at very low levels in the near-term fetal metanephros. Postnatally, renal kallikrein activity peaked immediately after birth and again at the time of weaning (P < 0.05 vs. other age groups) and remained high in the adult. Mature female rat kidneys contained 30% more active kallikrein than male kidneys (P < 0.05). The SBTI-sensitive D-VLR-AMC hydrolytic activity (due to serine proteases other than tissue kallikrein) accounted for 36-53% of the total renal amidolytic activity. Compared with the 5-day-old newborn, steady-state renal kallikrein mRNA levels increased threefold by day 12 and sixfold by adulthood. Run-on transcription analysis of renal cell nuclei revealed a significant increase in kallikrein gene transcription rate of 80% on day 12 (P < 0.05) and 480% in the adult (P < 0.001). The presence of active kallikrein in the developing kidney and the upregulation of its synthesis at specific time points during postnatal development implicate intrarenal kinins as potential modulators of renal growth and functional maturation.(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.

scholarly journals Tissue kallikrein deficiency, insulin resistance, and diabetes in mouse and man

2014 ◽  
Vol 221 (2) ◽  
pp. 297-308 ◽  
Author(s):  
Louis Potier ◽  
Ludovic Waeckel ◽  
Fréderic Fumeron ◽  
Sophie Bodin ◽  
Marinos Fysekidis ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Tissue Kallikrein ◽  
Loss Of Function ◽  
Kinin System ◽  
Angiotensin I Converting Enzyme ◽  
General Population Cohort ◽  
Kallikrein Kinin System ◽  
Changes Over Time

The kallikrein–kinin system has been suggested to participate in the control of glucose metabolism. Its role and the role of angiotensin-I-converting enzyme, a major kinin-inactivating enzyme, are however the subject of debate. We have evaluated the consequence of deficiency in tissue kallikrein (TK), the main kinin-forming enzyme, on the development of insulin resistance and diabetes in mice and man. Mice with inactivation of theTKgene were fed a high-fat diet (HFD) for 3 months, or crossed with obese, leptin-deficient (ob/ob) mice to generate doubleob/ob-TK-deficient mutants. In man, a loss-of-function polymorphism of theTKgene (R53H) was studied in a large general population cohort tested for insulin resistance, the DESIR study (4843 participants, 9 year follow-up). Mice deficient in TK gained less weight on the HFD than their WT littermates. Fasting glucose level was increased and responses to glucose (GTT) and insulin (ITT) tolerance tests were altered at 10 and 16 weeks on the HFD compared with standard on the diet, but TK deficiency had no influence on these parameters. Likewise,ob-TK−/−mice had similar GTT and ITT responses to those ofob-TK+/+mice. TK deficiency had no effect on blood pressure in either model. In humans, changes over time in BMI, fasting plasma glucose, insulinemia, and blood pressure were not influenced by the defective53H-coding TK allele. The incidence of diabetes was not influenced by this allele. These data do not support a role for the TK-kinin system, protective or deleterious, in the development of insulin resistance and diabetes.

Localization and secretion of tissue kallikrein in peptidoglycan-induced enterocolitis in Lewis rats

1998 ◽  
Vol 275 (4) ◽  
pp. G854-G861 ◽  
Author(s):  
Antoni Stadnicki ◽  
Julie Chao ◽  
Iwona Stadnicka ◽  
Eric Van Tol ◽  
Kuei-Fu Lin ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Rnase Protection Assay ◽  
Experimental Colitis ◽  
Tissue Kallikrein ◽  
Mrna Levels ◽  
Kinin System ◽  
Rnase Protection ◽  
Lewis Rats ◽  
Kallikrein Kinin System

The plasma kallikrein-kinin system is a mediator of intestinal inflammation induced by peptidoglycan-polysaccharide from group A streptococci (PG-APS) in rats. In this study we investigated the participation of intestinal tissue kallikrein (ITK). Lewis rats were injected intramurally with PG-APS. ITK was visualized by immunohistochemical staining. Cecal ITK concentration was measured by radioimmunoassay, and gene expression was evaluated by RNase protection assay. Kallikrein-binding protein (KBP) was evaluated in plasma by ELISA. Tissue kallikrein was identified in cecal goblet cells in both control and PG-APS-injected rats and in macrophages forming granulomas in inflamed tissues. Cecal ITK was significantly lower in acute and chronic phases of inflammation and in supernatant from in vitro cultures of inflamed cecum. ITK mRNA levels were not significantly different. Plasma KBP levels were significantly reduced in inflamed rats. The presence of tissue kallikrein in macrophages suggests participation in experimental colitis. The decrease of ITK in the inflamed intestine associated with unchanged mRNA levels suggests ITK release during intestinal inflammation.

Differential regulation of kallikrein, kininogen, and kallikrein-binding protein in arterial hypertensive rats

1996 ◽  
Vol 271 (1) ◽  
pp. F78-F86 ◽  
Author(s):  
C. Chao ◽  
P. Madeddu ◽  
C. Wang ◽  
Y. Liang ◽  
L. Chao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Binding Protein ◽  
Tap Water ◽  
Protective Action ◽  
Treated Group ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Kinin System ◽  
Renal Kallikrein

This study was designed to determine whether the kallikrein-kinin system exerts a protective action in hypertension induced by chronic inhibition of nitric oxide synthase. N omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/100 ml water) was given orally to Sprague-Dawley rats, while controls received regular tap water. Hepatic kininogen mRNA levels in the L-NAME-treated group were 2.9- and 2.5-fold higher at 3 and 4 wk, respectively, compared with control rats, whereas kallikrein-binding protein (KBP) mRNA levels were 82% and 45% of the values found in control rats at 3 and 4 wk, respectively. There was no significant change in hepatic alpha 1-antitrypsin mRNA levels under the same conditions. At 3 and 4 wk post L-NAME treatment, renal kallikrein mRNA levels were 2.5- and 3.4-fold higher than in controls, whereas renal beta-actin mRNA levels were similar between groups. Changes in the transcript levels of renal kallikrein, kininogen, and KBP were consistent with their protein levels. Immunoreactive total kininogen and low-Mr kininogen levels in sera and tissue kallikrein levels in kidney were significantly higher in the L-NAME-treated group, whereas KBP levels in the circulation were lower compared with controls. Systolic blood pressure was increased by 58 +/- 4 mmHg after 4 wk of L-NAME treatment. This effect was enhanced in rats given L-NAME in combination with HOE-140, a bradykinin B2-receptor antagonist, at the dose of 100 micrograms/day ip (79 +/- 5 vs. 58 +/- 4 mmHg, P < 0.05). This difference was confirmed by direct measurement of mean blood pressure (MBP). An intra-arterial bolus injection of 200 ng bradykinin significantly decreased MBP of L-NAME-treated rats, and this effect was blunted in the group treated with the bradykinin antagonist (-29 +/- 3 vs. -9 +/- 2 mmHg, P < 0.01). These results suggest that enhanced kallikrein and kininogen synthesis may have a protective role against the cardiovascular effects induced by chronic inhibition of nitric oxide synthesis.

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