scholarly journals Kinins and Kinin Receptors in Cardiovascular and Renal Diseases

2021 ◽  
Vol 14 (3) ◽  
pp. 240
Author(s):  
Jean-Pierre Girolami ◽  
Nadine Bouby ◽  
Christine Richer-Giudicelli ◽  
Francois Alhenc-Gelas
Keyword(s):  
Experimental Studies ◽  
Physiological Role ◽  
Renal Diseases ◽  
Kinin System ◽  
Genetic Studies ◽  
Pharmacological Manipulation ◽  
Kininase Ii ◽  
Kinin Receptors ◽  
Kallikrein Kinin System

This review addresses the physiological role of the kallikrein–kinin system in arteries, heart and kidney and the consequences of kallikrein and kinin actions in diseases affecting these organs, especially ischemic and diabetic diseases. Emphasis is put on pharmacological and genetic studies targeting kallikrein; ACE/kininase II; and the two kinin receptors, B1 (B1R) and B2 (B2R), distinguished through the work of Domenico Regoli and his collaborators. Potential therapeutic interest and limitations of the pharmacological manipulation of B1R or B2R activity in cardiovascular and renal diseases are discussed. This discussion addresses either the activation or inhibition of these receptors, based on recent clinical and experimental studies.

Development of diabetic cardiomyopathy and the kallikrein-kinin system – new insights from B1 and B2 receptor signaling

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Carsten Tschöpe ◽  
Dirk Westermann
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Calcium Handling ◽  
Kinin System ◽  
Cardiac Inflammation ◽  
B1 Receptor ◽  
Kinin Receptors ◽  
Patients With Diabetes ◽  
Underlying Mechanisms ◽  
Kallikrein Kinin System

Abstract Diabetic cardiomyopathy is a specific cardiomyopathy which develops in patients with diabetes mellitus in the absence of coronary atherosclerosis and hypertension. Despite the potential importance of this disease entity, the underlying mechanisms are only incompletely understood. Changes in calcium handling, disruption of the extracellular matrix regulation with accumulation of cardiac collagen, and furthermore cardiac inflammation may be an important mediator of this disease. This brief review focuses on the current aspects of the kallikrein-kinin system and its influence on the development of diabetic cardiomyopathy with particular regard to the kinin receptors B1 and B2, as their role in the development of this disease is still under discussion. Whether the role of the B1 receptor is similar to the well-described beneficial role of the B2 receptor or whether its function is opposed to the B2 receptor is controversial. Some recent findings suggest that the B1 receptor mediates cardiac inflammation and therefore may be detrimental for cardiac function in the setting of diabetic cardiomyopathy.

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

2003 ◽  
Vol 285 (1) ◽  
pp. R1-R13 ◽  
Author(s):  
Alvin H. Schmaier
Keyword(s):  
Cross Talk ◽  
Physiological Role ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Kinin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Two Systems ◽  
Kallikrein Kinin System

Understanding the physiological role of the plasma kallikrein-kinin system (KKS) has been hampered by not knowing how the proteins of this proteolytic system, when assembled in the intravascular compartment, become activated under physiological conditions. Recent studies indicate that the enzyme prolylcarboxypeptidase, an ANG II inactivating enzyme, is a prekallikrein activator. The ability of prolylcarboxypeptidase to act in the KKS and the renin-angiotensin system (RAS) indicates a novel interaction between these two systems. This interaction, along with the roles of angiotensin converting enzyme, cross talk between bradykinin and angiotensin-( 1 – 7 ) action, and the opposite effects of activation of the ANG II receptors 1 and 2 support a hypothesis that the plasma KKS counterbalances the RAS. This review examines the interaction and cross talk between these two protein systems. This analysis suggests that there is a multilayered interaction between these two systems that are important for a wide array of physiological functions.

Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man

2013 ◽  
Vol 110 (09) ◽  
pp. 476-483 ◽  
Author(s):  
Ludovic Waecke ◽  
Louis Potier ◽  
Christine Richer ◽  
Ronan Roussel ◽  
Nadine Bouby ◽  
...  
Keyword(s):  
Human Subjects ◽  
Physiological Role ◽  
Tissue Kallikrein ◽  
Site Mutation ◽  
Cardiac Ischaemia ◽  
Kinin Receptors ◽  
At1 Receptor Antagonists ◽  
Kallikrein Activity ◽  
Deficient Mice

SummaryStudy of mice rendered deficient in tissue kallikrein (TK) by gene inactivation and human subjects partially deficient in TK activity as consequence of an active site mutation has allowed recognising the physiological role of TK and its peptide products kinins in arterial function and in vasodilatation, in both species. TK appears as the major kinin forming enzyme in arteries, heart and kidney. Non-kinin mediated actions of TK may occur in epithelial cells in the renal tubule. In basal condition, TK deficiency induces mild defective phenotypes in the cardiovascular system and the kidney. However, in pathological situations where TK synthesis is typically increased and kinins are produced, TK deficiency has major, deleterious consequences. This has been well documented experimentally for cardiac ischaemia, diabetes renal disease, peripheral ischaemia and aldosterone-salt induced hypertension. These conditions are all aggravated by TK deficiency. The beneficial effect of ACE/kininase II inhibitors or angiotensin II AT1 receptor antagonists in cardiac ischaemia is abolished in TK-deficient mice, suggesting a prominent role for TK and kinins in the cardioprotective action of these drugs. Based on findings made in TK-deficient mice and additional evidence obtained by pharmacological or genetic inactivation of kinin receptors, development of novel therapeutic approaches relying on kinin receptor agonism may be warranted.

Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammation

1991 ◽  
Vol 260 (2) ◽  
pp. G213-G219 ◽  
Author(s):  
R. A. DeLa Cadena ◽  
K. J. Laskin ◽  
R. A. Pixley ◽  
R. B. Sartor ◽  
J. H. Schwab ◽  
...  
Keyword(s):  
Cell Wall ◽  
Acute Phase ◽  
Bacterial Cell ◽  
Chronic Phase ◽  
Bacterial Cell Wall ◽  
Kinin System ◽  
Kallikrein Kinin System ◽  
Bacterial Products

The plasma kallikrein-kinin system is activated in Gram-negative sepsis and typhoid fever, two diseases in which bacterial products have been shown to initiate inflammation. Because a single intraperitoneal injection of bacterial cell wall peptidoglycan-polysaccharide polymers from group A steptococci (PG-APS) into a Lewis rat produces a syndrome of relapsing polyarthritis and anemia, we investigated changes in the role of the kallikrein-kinin system in this model of inflammation. Coagulation studies after injection of PG-APS revealed an immediate and persistent decrease in prekallikrein levels. High-molecular-weight kininogen levels decreased significantly during the acute phase and correlated with the severity of arthritis. Factor XI levels were decreased only during the acute phase. Antithrombin III levels remained unchanged, indicating that neither decreased hepatic synthesis nor disseminated intravascular coagulation caused the decreased plasma contact factors. Plasma T-kininogen (an acute phase protein) was significantly elevated during the chronic phase. PG-APS failed to activate the contact system in vitro. Thus the kallikrein-kinin system plays an important role in this experimental model of inflammation, suggesting that activation of this system may play a role in the pathogenesis of inflammatory bowel disease and rheumatoid arthritis in which bacterial products might be etiologically important.

The dual role of the contact system in bacterial infectious disease

2007 ◽  
Vol 98 (09) ◽  
pp. 497-502 ◽  
Author(s):  
Inga-Maria Frick ◽  
Lars Björck ◽  
Heiko Herwald
Keyword(s):  
Vascular Endothelium ◽  
Blood Cells ◽  
State Of The Art ◽  
Contact System ◽  
Intrinsic Pathway ◽  
Kinin System ◽  
Inflammatory Reactions ◽  
Bacterial Infectious Disease ◽  
Kallikrein Kinin System

SummaryHemostasis is a sensitive and tightly regulated process, involving the vascular endothelium and blood cells as well as factors of the coagulation and fibrinolytic cascades. Over the last four decades evidence has accumulated that during infection, inflammatory mediators from the microbe and/or host are capable to modulate the equilibrium between the procoagulant and anticoagulant status of the host. Dependent on the mode of activation, these changes can cause either local or systemic inflammatory reactions that may be beneficial or deleterious to the human host. The present review aims to present the state of the art with respect to the role of the contact system (also known as the intrinsic pathway of coagulation or the kallikrein/kinin system) in innate immunity and systemic inflammatory reactions.

scholarly journals Antihypertensive effect of MK-421 in rats. Role of the renal kallikrein-kinin system.

Hypertension ◽  
1984 ◽  
Vol 6 (2_pt_1) ◽  
pp. 229-235 ◽  
Author(s):  
M Yasujima ◽  
K Abe ◽  
M Tanno ◽  
Y Kasai ◽  
J Tajima ◽  
...  
Keyword(s):  
Antihypertensive Effect ◽  
Kinin System ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System

scholarly journals A Role of Inflammation and Immunity in Essential Hypertension—Modeled and Analyzed Using Petri Nets

2020 ◽  
Vol 21 (9) ◽  
pp. 3348
Author(s):  
Dorota Formanowicz ◽  
Agnieszka Rybarczyk ◽  
Marcin Radom ◽  
Piotr Formanowicz
Keyword(s):  
Essential Hypertension ◽  
Adaptive Immune System ◽  
Low Grade ◽  
Kinin System ◽  
Reactive Protein ◽  
Adaptive Immune ◽  
Key Enzyme ◽  
Kallikrein Kinin System ◽  
Low Grade Inflammation

Recent studies have shown that the innate and adaptive immune system, together with low-grade inflammation, may play an important role in essential hypertension. In this work, to verify the importance of selected factors for the development of essential hypertension, we created a Petri net-based model and analyzed it. The analysis was based mainly on t-invariants, knockouts of selected fragments of the net and its simulations. The blockade of the renin-angiotensin (RAA) system revealed that the most significant effect on the emergence of essential hypertension has RAA activation. This blockade affects: (1) the formation of angiotensin II, (2) inflammatory process (by influencing C-reactive protein (CRP)), (3) the initiation of blood coagulation, (4) bradykinin generation via the kallikrein-kinin system, (5) activation of lymphocytes in hypertension, (6) the participation of TNF alpha in the activation of the acute phase response, and (7) activation of NADPH oxidase—a key enzyme of oxidative stress. On the other hand, we found that the blockade of the activation of the RAA system may not eliminate hypertension that can occur due to disturbances associated with the osmotically independent binding of Na in the interstitium. Moreover, we revealed that inflammation alone is not enough to trigger primary hypertension, but it can coexist with it. We believe that our research may contribute to a better understanding of the pathology of hypertension. It can help identify potential subprocesses, which blocking will allow better control of essential hypertension.

Antidipsogenic effects of eel bradykinins in the eelAnguilla japonica

2001 ◽  
Vol 281 (4) ◽  
pp. R1090-R1096 ◽  
Author(s):  
Yoshio Takei ◽  
Takamasa Tsuchida ◽  
Zhihong Li ◽  
J. Michael Conlon
Keyword(s):  
Dose Range ◽  
Plasma Concentrations ◽  
Plasma Osmolality ◽  
Physiological Role ◽  
Kinin System ◽  
Arterial Blood ◽  
Dependent Inhibition ◽  
High Conservation ◽  
Kallikrein Kinin System ◽  
Sustained Increase

A peptide with bradykinin (BK)-like immunoreactivity was isolated from an incubate of heat-denatured eel plasma with porcine pancreatic kallikrein. The purified peptide had the following amino acid sequence: Arg-Arg-Pro-Pro-Gly-Ser-Trp-Pro-Leu-Arg. This decapeptide, named eel [Arg0]BK, was identical to two previously identified BK homologs from cod and trout. High conservation of the BK sequence among distant teleost species suggests an important function in this vertebrate group. Bolus intra-arterial injections of eel [Arg0]BK, BK, and [Arg0]-des-Arg9-BK (1–10 nmol/kg) caused significant ( P < 0.05) inhibition of drinking in seawater-adapted eels. The potency of the inhibition was ranked in the following order: [Arg0]BK > [Arg0]-des-Arg9-BK = BK. The BK peptides also produced an immediate, transient increase followed by a sustained increase in arterial blood pressure and an initial decrease followed by an increase in heart rate. Strong tachyphylaxis occurred for the cardiovascular effect but not for the antidipsogenic effect. The order of the potency of the cardiovascular actions, [Arg0]BK > BK > [Arg0]-des-Arg9-BK, was different from that of the antidipsogenic action. Slow infusions of eel [Arg0]BK in the dose range 1–1,000 pmol · kg−1 · min−1 produced concentration-dependent inhibition of drinking without changes in arterial pressure, plasma osmolality, and hematocrit. At the infusion rate of >100 pmol · kg−1 · min−1, plasma concentrations of angiotensin II, a potent dipsogenic hormone in eels, increased, suggesting an interaction of the kallikrein-kinin and renin-angiotensin systems. In mammals, BK is dipsogenic and vasodepressor, so that our data demonstrate opposite effects on fluid and cardiovascular regulation of BK in the eel and suggest a new physiological role for the kallikrein-kinin system in teleost fish.

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