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.

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 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.

Role of renin-angiotensin system in glucocorticoid hypertension in rats

1982 ◽  
Vol 243 (1) ◽  
pp. E48-E51 ◽  
Author(s):  
H. Suzuki ◽  
M. Handa ◽  
K. Kondo ◽  
T. Saruta
Keyword(s):  
Blood Pressure ◽  
Intravenous Injection ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Dependent Manner ◽  
Concurrent Administration ◽  
Angiotensin System ◽  
Renin Angiotensin

The role of the renin-angiotensin system in the regulation of the blood pressure of dexamethasone-treated rats (Dex) was evaluated using saralasin, an angiotensin II antagonist, and SQ 14225 (SQ) (d-3-mercapto-2-methylpropranoyl-1-proline), an angiotensin-converting enzyme inhibitor. During a 7-day period blood pressure rose 65 +/- 10 mmHg (P less than 0.001) in Dex with no significant changes in plasma renin activity. Concurrent administration of dexamethasone and SQ attenuated the elevation of blood pressure (P less than 0.05). In the conscious, freely moving state, intravenous injection of SQ (10, 30, 100 micrograms/kg) reduced blood pressure of DEX in a dose-dependent manner (P less than 0.05). Also, intravenous injection of saralasin (10 micrograms.kg-1 . min-1) reduced blood pressure significantly (P less than 0.01). Bilateral nephrectomy abolished the effects of saralasin and SQ on blood pressure in Dex. These results indicate that the elevation of blood pressure in DEX depends partially on the renin-angiotensin 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.

scholarly journals Role of adenosine in dialysis-induced hypotension.

1994 ◽  
Vol 4 (12) ◽  
pp. 1987-1994 ◽  
Author(s):  
T Shinzato ◽  
M Miwa ◽  
S Nakai ◽  
H Morita ◽  
H Odani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adenosine Receptor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Plasma Norepinephrine ◽  
Angiotensin System ◽  
Induced Hypotension ◽  
Adenosine Receptor Antagonist ◽  
Hemodialysis Session

First, this investigation showed that plasma levels of inosine, hypoxanthine, and xanthine, which are metabolites of adenosine, rose sharply when blood pressure dropped suddenly along with symptoms during a hemodialysis session (sudden hypotension), but not when it decreased gradually with eventual symptoms (gradual hypotension). Because adenosine has an action to dilate vessels, this result indicates the possibility that the increased release of adenosine would be a cause of sudden hypotension. Second, it was found that the frequency of sudden hypotension decreases with the administration of caffeine, which is an adenosine-receptor antagonist, whereas the frequency of gradual hypotension did not change. This result supports the above-mentioned hypothesis that adenosine may well be a mediator of sudden hypotension, but not of gradual hypotension. Third, our investigation demonstrated no significant differences in plasma norepinephrine level, in plasma renin activity, or in mean blood pressure between the hemodialysis session in which caffeine was administered and the session in which a placebo was given. These findings suggest that the effect of caffeine administration to prevent sudden hypotension is not mediated by the stimulation of the sympathetic nervous system or activation of the renin-angiotensin system, but by the adenosine-receptor antagonism.

Effects of nonhypotensive endotoxemia in conscious rats: role of prostaglandins

1988 ◽  
Vol 254 (3) ◽  
pp. H509-H516 ◽  
Author(s):  
M. Burnier ◽  
B. Waeber ◽  
J. F. Aubert ◽  
J. Nussberger ◽  
H. R. Brunner
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Plasma Renin Activity ◽  
Renal Blood Flow ◽  
Plasma Renin ◽  
Renin Activity ◽  
Plasma Norepinephrine ◽  
Plasma Catecholamine ◽  
Conscious Rats

A nonhypotensive dose of endotoxin was administered to normal conscious rats to evaluate the vascular and humoral effects of endotoxemia per se. Mean blood pressure and heart rate remained stable during the 45 min infusion of Escherichia coli endotoxin (0.01 mg/min). However, a marked increase in plasma renin activity (4.2 +/- 0.48 vs. 30.2 +/- 6 ng.ml-1.h-1, mean +/- SE, P less than 0.01), plasma epinephrine (0.112 +/- 0.04 vs. 1.71 +/- 0.5 ng/ml, P less than 0.01), and plasma norepinephrine (0.269 +/- 0.028 vs. 1.3 +/- 0.2 ng/ml, P less than 0.001) was observed during infusion in endotoxin-treated rats when compared with the vehicle-treated animals. In addition, the blood pressure response to exogenous norepinephrine was significantly reduced during nonhypotensive endotoxemia. Significant changes in regional blood flow distribution, as assessed by radiolabeled microspheres, were observed in endotoxemic rats; in particular a decrease in renal blood flow (7.39 +/- 0.43 vs. 5.97 +/- 0.4 ml.min-1.g-1, P less than 0.05) and an increase in coronary blood flow (5.01 +/- 0.38 vs. 6.44 +/- 0.33 ml.min-1.g-1, P less than 0.01) were found. The role of prostaglandins in the vascular and humoral alterations induced by nonhypotensive endotoxemia was also examined. Pretreatment with indomethacin (5 mg) prevented the increase in plasma renin activity as well as plasma catecholamine levels. On the contrary, the decreased vascular reactivity and the reduction in renal blood flow observed during endotoxemia were not affected by prostaglandin synthesis inhibition. Thus significant vascular and humoral changes have been found during endotoxemia even in absence of hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Role of the Kallikrein-Kinin System Genes in the Salt Sensitivity of Blood Pressure

2012 ◽  
Vol 176 (suppl_7) ◽  
pp. S72-S80 ◽  
Author(s):  
Dongfeng Gu ◽  
Qi Zhao ◽  
Tanika N. Kelly ◽  
James E. Hixson ◽  
Dabeeru C. Rao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Sensitivity ◽  
Kinin System ◽  
Kallikrein Kinin System

scholarly journals Role of ACE2 in pregnancy and potential implications for COVID-19 susceptibility

2021 ◽  
Vol 135 (15) ◽  
pp. 1805-1824
Author(s):  
Nayara Azinheira Nobrega Cruz ◽  
Danielle Stoll ◽  
Dulce Elena Casarini ◽  
Mariane Bertagnolli
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Renin Angiotensin System ◽  
Current Evidence ◽  
Maternal Circulation ◽  
Disease Manifestation ◽  
Kinin System ◽  
Kallikrein Kinin System ◽  
The Impact

Abstract In times of coronavirus disease 2019 (COVID-19), the impact of severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection on pregnancy is still unclear. The presence of angiotensin-converting enzyme (ACE) 2 (ACE2), the main receptor for SARS-CoV-2, in human placentas indicates that this organ can be vulnerable for viral infection during pregnancy. However, for this to happen, additional molecular processes are critical to allow viral entry in cells, its replication and disease manifestation, particularly in the placenta and/or feto–maternal circulation. Beyond the risk of vertical transmission, COVID-19 is also proposed to deplete ACE2 protein and its biological actions in the placenta. It is postulated that such effects may impair essential processes during placentation and maternal hemodynamic adaptations in COVID-19 pregnancy, features also observed in several disorders of pregnancy. This review gathers information indicating risks and protective features related to ACE2 changes in COVID-19 pregnancies. First, we describe the mechanisms of SARS-CoV-2 infection having ACE2 as a main entry door and current evidence of viral infection in the placenta. Further, we discuss the central role of ACE2 in physiological systems such as the renin–angiotensin system (RAS) and the kallikrein–kinin system (KKS), both active during placentation and hemodynamic adaptations of pregnancy. Significant knowledge gaps are also identified and should be urgently filled to better understand the fate of ACE2 in COVID-19 pregnancies and the potential associated risks. Emerging knowledge will be able to improve the early stratification of high-risk pregnancies with COVID-19 exposure as well as to guide better management and follow-up of these mothers and their children.

Haemodynamic role of vasopressin released during Finnish sauna

1986 ◽  
Vol 112 (2) ◽  
pp. 166-171 ◽  
Author(s):  
J. P. Bussien ◽  
R. C. Gaillard ◽  
J. Nussberger ◽  
B. Waeber ◽  
K. G. Hofbauer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Skin Blood Flow ◽  
Plasma Osmolality ◽  
Plasma Renin ◽  
Plasma Norepinephrine ◽  
Hot Air ◽  
Simultaneous Change

Abstract. The effect of vasopressin released during Finnish sauna on blood pressure, heart rate and skin blood flow was investigated in 12 healthy volunteers. Exposure to the hot air decrease body weight by 0.6 to 1.25 kg (mean = 0.8 kg, P < 0.001). One hour after the end of the sauna sessions, plasma vasopressin was higher (1.7 ± 0.2 pg/ml, P < 0.01 mean ± sem) than before the sauna (1.0 ± 0.1 pg/ml). No simultaneous change in plasma osmolality, plasma renin activity, plasma norepinephrine, epinephrine, cortisol, aldosterone, beta-endorphin and metenkephalin levels was observed. Despite the slight sauna-induced elevation in circulating vasopressin, intravenous injection of the specific vascular vasopressin antagonist d(CH2)5Tyr-(Me)AVP (5 μg/kg) 1 h after the sauna had no effect on blood pressure, heart rate or skin blood flow. These data suggest that vasopressin released into the circulation during a sauna session reaches concentrations which are not high enough to interfere directly with vascular tone.

Hypertension after ending captopril administration: pathogenesis in 2-kidney, 1-clip rat

1984 ◽  
Vol 247 (6) ◽  
pp. H946-H951
Author(s):  
J. M. DeForrest ◽  
J. S. Creekmore ◽  
R. A. Ferrone
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Severe Hypertension ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Kinin System ◽  
Series Of Experiments ◽  
Sympathetic Nervous ◽  
Kallikrein Kinin System ◽  
Prostaglandin System

We have previously shown that continuous captopril administration prevents hypertension from developing in the two-kidney, one-clip (2K, 1C) rat. The present investigation was designed to determine the mechanism(s) producing the hypertension. In one series of experiments captopril prevented pressure from increasing during an 8-wk treatment period. Relative to the last day of treatment, mean arterial pressure and total peripheral resistance (TPR) were increased and cardiac output was unchanged at 3, 7, and 28 days after captopril cessation. Plasma renin activity (PRA) was unchanged 3, 7, and 14 days after captopril cessation but was elevated at 28, 49, and 56 days after captopril cessation only in 2K, 1C rats with severe hypertension (systolic blood pressure greater than 180 mmHg). Guanethidine (45 mg/kg po, bid) did not prevent the development of 2K, 1C hypertension but did prevent the hypertension from developing after cessation of captopril. Blockade of the prostaglandin system with indomethacin (5 mg/kg + 50 micrograms X kg-1 X min-1) and of the kallikrein-kinin system with aprotinin (25,000 KIU + 150 KIU X kg-1 X min-1) for 2 h had no effect on captopril's antihypertensive effect. Additionally, no change in sodium or water balance was observed after captopril cessation. Taken together these data demonstrate that hypertension after captopril cessation is due to an increase in TPR. Additionally, the rise in TPR is due to both the sympathetic nervous and the renin-angiotensin systems since both systems must be functional before pressure rises.

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