The Kallikrein—Kinin System in Asthma and Acute Respiratory Distress Syndrome

Farmer, Stephen G.

doi:10.1016/b978-012249340-9/50017-6

Cited by 13 publications

(9 citation statements)

References 142 publications

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“…Role of vascular effects in reflex bronchospasm evoked by histamine and bradykinin. Histamine and bradykinin can evoke airway smooth muscle contraction but also relaxation of pulmonary vascular smooth muscle (2,14,31). The effects of histamine and bradykinin on the vasculature are mediated indirectly through formation of prostanoids and nitric oxide, both of which are thought to modulate and/or activate airway afferent nerves.…”

Section: Resultsmentioning

confidence: 99%

“…Three lines of experimental evidence indicate that histamine and bradykinin initiate reflex bronchospasm by activating distinct airway afferent nerve subtypes and do so by distinct mechanisms. First, bradykinin, unlike histamine, is a direct stimulant of tachykinincontaining vagal afferent nerves in vitro, whereas it has no direct effects on RARs innervating the trachea, larynx, and bronchi and has only subtle, direct effects on airway smooth muscle (9,14,21,35,38). Tachykinin-receptor antagonists were without effect on baseline TT or histamine-induced increases in TT but abolished reflexes initiated by bradykinin (when cyclooxygenase was also inhibited).…”

Section: Discussionmentioning

confidence: 99%

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Multiple mechanisms of reflex bronchospasm in guinea pigs

Canning¹,

Reynolds²,

Mazzone³

2001

Journal of Applied Physiology

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The mechanisms of histamine- and bradykinin-induced reflex bronchospasm were determined in anesthetized guinea pigs. With intravenous administration, both autacoids evoked dose-dependent increases in tracheal cholinergic tone. Vagotomy or atropine prevented these tracheal reflexes. When delivered as an aerosol, bradykinin readily increased tracheal cholinergic tone, whereas histamine aerosols were much less effective at inducing tracheal reflexes. Also, unlike histamine, bradykinin could evoke profound increases in cholinergic tone without directly or indirectly (e.g., prostanoid dependent) inducing measurable airway smooth muscle contraction resulting in bronchospasm. Neither autacoid required de novo synthesis of prostanoids or nitric oxide to induce reflex tracheal contractions. Combined cyclooxygenase inhibition and tachykinin-receptor antagonism did, however, abolish all effects of bradykinin in the airways, whereas responses to histamine were unaffected by these pretreatments. The data indicate that histamine and bradykinin initiate reflex bronchospasm by differential activation of vagal afferent nerve subtypes. We speculate that selective activation of either airway C fibers or airway rapid adapting receptors can initiate reflex bronchospasm.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Multiple mechanisms of reflex bronchospasm in guinea pigs

Canning¹,

Reynolds²,

Mazzone³

2001

Journal of Applied Physiology

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“…Bradykinin is thought to be a potent inflammatory mediator involved in acute lung injury, ARDS and systemic inflammatory response syndrome (SIRS) that are associated with conditions such as sepsis, immune-mediated lung injury, and multiple trauma [22,23]. BK, consisting of nine amino acids, is a major kinin with welldocumented pharmacological properties including vasodilatation and vascular leakage.…”

Section: Discussionmentioning

confidence: 99%

Bradykinin stimulates IL-6 and IL-8 production by human lung fibroblasts through ERK- and p38 MAPK-dependent mechanisms

Hayashi¹,

Yamashita

Matsui

et al. 2000

Eur Respir J

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Bradykinin (BK) is a major kinin with well-documented pharmacological properties including vascular leakage and induction of a variety of cytokines. However, the intracellular signalling mechanisms by which BK induced proinflammatory cytokine production have not been fully elucidated. This study investigated the role of the extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (p38 MAPK) in the BK-induced interleukin (IL)-6 and IL-8 production by human lung fibroblasts.Lung fibroblasts were stimulated with BK in the presence or in the absence of PD98059, a specific MAPK/ERK kinase-1 inhibitor, or SB203580, a specific p38 MAPK inhibitor, and IL-6 or IL-8 production and their gene expression was examined. BK-induced ERK 1/2 or p38 MAPK phosphorylation was also analysed by Western blot analysis.BK at nanomolar concentrations stimulated lung fibroblasts to produce IL-6 and IL-8 along with increased ERK 1/2 and p38 MAPK phosphorylation. BK-induced IL-6 and IL-8 synthesis was inhibited by a B2-type BK receptor antagonist. Furthermore, PD98059 or SB203580 significantly suppressed BK-induced IL-6 and IL-8 production and their gene expression.These results indicate that bradykinin-induced interleukin-6 and interleukin-8 production are at least partly mediated through the extracellular signal-related protein kinase 1/2 and p38 mitogen-activated protein kinase pathway-dependent activation in human lung fibroblasts, and suggest that bradykinin appears to be involved in the inflammatory reaction leading to acute lung injury through stimulating interleukin-6 and interleukin-8 production by lung fibroblasts. Eur Respir J 2000; 16: 452±458.

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“…Furthermore, components of the KKS are also found in inflammatory exudates [for a review, see (97)]. Thus, it has been proposed that various components of the KKS are mediators and/or modulators of inflammation in arthritis (54, 63, 263) [for a review, see (166)], pancreatitis (322), skin inflammation (209), asthma (78), rhinitis (71), allergic diseases (71), hereditary angioedema (71), sepsis (211), colitis (99, 156), and many other diseases [for a review, see (1,176)].…”

Section: The Physiological Role Of the Kallikrein-kinin Systemmentioning

confidence: 99%

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

Rhaleb

Yang

Carretero

2011

Comprehensive Physiology

107

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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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The Kallikrein—Kinin System in Asthma and Acute Respiratory Distress Syndrome

Cited by 13 publications

References 142 publications

Multiple mechanisms of reflex bronchospasm in guinea pigs

Multiple mechanisms of reflex bronchospasm in guinea pigs

Bradykinin stimulates IL-6 and IL-8 production by human lung fibroblasts through ERK- and p38 MAPK-dependent mechanisms

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

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