The Kallikrein-Kinin System in Inflammation

Kaplan, Allen P.; Silverberg, Mark; Ghebrehiwet, Berhane; Atkins, Paul C.; Zweiman, Burton

doi:10.1007/978-1-4615-9543-4_18

Cited by 12 publications

(3 citation statements)

References 33 publications

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“…All kininogens, including LMWK, HMWK, and t-kininogen, also inhibit thiol proteases such as cathepsin M, H, and calpains (16, 86, 193, 194). HMWK is involved in the early stages of surface-activated coagulation (intrinsic coagulation pathway) (69, 120, 277). …”

Section: Introductionmentioning

confidence: 99%

The Kallikrein‐Kinin System as a Regulator of Cardiovascular and Renal Function

Rhaleb

Yang

Carretero

2011

Comprehensive Physiology

108

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Autocrine, paracrine, endocrine, and neuroendocrine hormonal systems help regulate cardiovascular and renal function. Any change in the balance among these systems may result in hypertension and target organ damage, whether the cause is genetic, environmental or a combination of the two. Endocrine and neuroendocrine vasopressor hormones such as the renin-angiotensin system (RAS), aldosterone, and catecholamines are important for regulation of blood pressure and pathogenesis of hypertension and target organ damage. While the role of vasodepressor autacoids such as kinins is not as well defined, there is increasing evidence that they are not only critical to blood pressure and renal function but may also oppose remodeling of the cardiovascular system. Here we will primarily be concerned with kinins, which are oligopeptides containing the aminoacid sequence of bradykinin. They are generated from precursors known as kininogens by enzymes such as tissue (glandular) and plasma kallikrein. Some of the effects of kinins are mediated via autacoids such as eicosanoids, nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and/or tissue plasminogen activator (†PA). Kinins help protect against cardiac ischemia and play an important part in preconditioning as well as the cardiovascular and renal protective effects of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor blockers (ARB). But the role of kinins in the pathogenesis of hypertension remains controversial. A study of Utah families revealed that a dominant kallikrein gene expressed as high urinary kallikrein excretion was associated with a decreased risk of essential hypertension. Moreover, researchers have identified a restriction fragment length polymorphism (RFLP) that distinguishes the kallikrein gene family found in one strain of spontaneously hypertensive rats (SHR) from a homologous gene in normotensive Brown Norway rats, and in recombinant inbred substrains derived from these SHR and Brown Norway rats this RFLP cosegregated with an increase in blood pressure. However, humans, rats and mice with a deficiency in one or more components of the kallikrein-kinin-system (KKS) or chronic KKS blockade do not have hypertension. In the kidney, kinins are essential for proper regulation of papillary blood flow and water and sodium excretion. B2-KO mice appear to be more sensitive to the hypertensinogenic effect of salt. Kinins are involved in the acute antihypertensive effects of ACE inhibitors but not their chronic effects (save for mineralocorticoidsalt-induced hypertension). Kinins appear to play a role in the pathogenesis of inflammatory diseases such as arthritis and skin inflammation; they act on innate immunity as mediators of inflammation by promoting maturation of dendritic cells, which activate the body’s adaptive immune system and thereby stimulate mechanisms that promote inflammation. On the other hand, kinins acting via NO contribute to the vascular protective effect of ACE inhibitors during neointima formation. In myocardial i...

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Section: Introductionmentioning

confidence: 99%

The Kallikrein‐Kinin System as a Regulator of Cardiovascular and Renal Function

Rhaleb

Yang

Carretero

2011

Comprehensive Physiology

108

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“…T-kinin, acting via B 2 receptors, is one of the main acute reactants of inflammation [41][42][43][44]. HMWK is involved in the early stages of surface-activated coagulation (intrinsic coagulation pathway) [8,10,45].…”

Section: Kininogens or Kallikrein Substratesmentioning

confidence: 99%

Role of Kinins in Hypertension and Heart Failure

et al. 2020

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The kallikrein–kinin system (KKS) is proposed to act as a counter regulatory system against the vasopressor hormonal systems such as the renin-angiotensin system (RAS), aldosterone, and catecholamines. Evidence exists that supports the idea that the KKS is not only critical to blood pressure but may also oppose target organ damage. Kinins are generated from kininogens by tissue and plasma kallikreins. The putative role of kinins in the pathogenesis of hypertension is discussed based on human mutation cases on the KKS or rats with spontaneous mutation in the kininogen gene sequence and mouse models in which the gene expressing only one of the components of the KKS has been deleted or over-expressed. Some of the effects of kinins are mediated via activation of the B2 and/or B1 receptor and downstream signaling such as eicosanoids, nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and/or tissue plasminogen activator (T-PA). The role of kinins in blood pressure regulation at normal or under hypertension conditions remains debatable due to contradictory reports from various laboratories. Nevertheless, published reports are consistent on the protective and mediating roles of kinins against ischemia and cardiac preconditioning; reports also demonstrate the roles of kinins in the cardiovascular protective effects of the angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor blockers (ARBs).

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“…Bradykinin, a vasoactive peptide released from precursor kininogens by a protease known as kallikrein [9], is an important component of both acute and chronic inflammatory processes [10, 11]. However, bradykinin performs several other biological functions as well.…”

Section: Introductionmentioning

confidence: 99%

Effects of bradykinin on the survival of multiterritory perforator flaps in rats

Wang

Chen

et al. 2019

World J Surg Onc

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Background Bradykinin, a vasoactive peptide, has many biological functions. For example, it accelerates angiogenesis. Thus, we studied the effects of bradykinin on the survival of perforator flaps. Methods Averagely, 50 male Sprague–Dawley rats were divided into control and bradykinin groups and underwent procedures to the multiterritory perforator flap. Areas of flap survival were tested 7 days later. Flap perfusion was evaluated by laser Doppler imaging. We assessed the extent of autophagy by determining LC3-II/I, Beclin 1, and p62. Flap angiogenesis was assessed by immunohistochemistry and H&E staining. We measured the level of vascular endothelial growth factor (VEGF) protein using western blot. We assessed oxidative stress by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) levels. The apoptotic index was also evaluated by western blot, and we determined nitric oxide (NO) production using an NO assay kit. Results The bradykinin group exhibited significantly larger areas of flap survival, higher blood supply, and more neovascularization. The bradykinin group also had higher SOD activity, higher VEGF expression and NO content, and reduced MDA compared to the control group. Rats treated with bradykinin also had lower levels of apoptosis and autophagy relative to the control group. Conclusion Our results suggest that bradykinin promotes the survival of multiterritory perforator flaps by increasing angiogenesis, promoting the release of NO, suppressing apoptosis, reducing oxidative stress, and inhibiting autophagy.

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The Kallikrein-Kinin System in Inflammation

Cited by 12 publications

References 33 publications

The Kallikrein‐Kinin System as a Regulator of Cardiovascular and Renal Function

The Kallikrein‐Kinin System as a Regulator of Cardiovascular and Renal Function

Role of Kinins in Hypertension and Heart Failure

Effects of bradykinin on the survival of multiterritory perforator flaps in rats

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