Kinins histamine

At the cellular level, eosinophils, mast cells, alveolar macrophages, lymphocytes and neutrophils recruited to the airways of asthmatics produce a variety of inflammatory mediators, such as histamine, kinins, neuropeptides, and leukotrienes, which lead to airway smooth muscle constriction and obstruction of airflow, and the perpetuation of airway inflammation [20, 21]. An understanding of the inflammatory processes and the molecular pathways of these mediators has led to the development and widespread use of several pharmacologic agents that mitigate airway inflammation and bronchoconstriction. 

Vasoactive substances (histamine, kinins, prostaglandins) are released at sites of inflammation, increasing blood flow and vascular permeability. This causes edema, warmth, erythema, and pain and makes it easier for granulocytes to pass from blood vessels to sites of inflammation. 

An immediate reaction occurs within seconds to minutes, resulting in the rapid release of preformed mediators and newly generated mediators from the arachidonic acid cascade. Mediators of immediate hypersensitivity include histamine, leukotrienes, prostaglandin, tryptase, and kinins. These mediators cause vasodilation, increased vascular permeability, and production of nasal secretions. Histamine produces rhinorrhea, itching, sneezing, and nasal obstruction. 

Figure 4.6. Log dose-response relationships for the effects of synthetic neurotensin, synthetic brady-kinin, and various preparations of NRP on the release of histamine from isolated rat mast cells [73], Each point is the mean obtained for two separate incubations.

Involvement of complement activation in the etiology of the acute byssinotic reaction could explain the pathogenic mechanism of histamine release, non-histamine-mediated bronchoconstriction, chemotaxis, endotoxin and bacterial proteolytic enzyme action. Bronchoconstriction experienced in the acute byssinotic reaction might be attributed to the combined action of C3a and C5a mediated histamine release and non-histamine mediated kinin activity. The presence of PMN in the nasal airways of byssinotics might be explained by the chemotactic action of C5a and the C567 complex. 

Adrenaline (epinephrine) is a sympathomimetic agent that causes bronchodilatation. It is used to relieve bronchospasm in anaphylactic shock reactions. Histamine, kinins and prostaglandins, such as prostaglandin E2, are inflammatory mediators. In response to allergic stimuli, inflammatory mediators may cause bronchoconstrictions. Guaifenesin is an expectorant preparation that increases bronchial secretions to promote the expulsion of the mucus coughed up. 

At the bronchi, predominantly /32-adrenoceptors are present on the smooth muscle cells. Therefor noradrenaline has hardly any influence on the muscular tonus whereas adrenaline induce a dilatation especially of precontracted bronchi, independent of the cause (histamine, acetylcholine, kinines, prostanoides). This effect can be used therapeutically in the therapy of bronchial asthma. In general the local application by aerosol is more useful than the systemic application, due to lesser side effects and the additional, beneficial effect of the reduction of mucosa swelling. 

The autacoids comprise histamine, serotonin, angiotensin, neurotensin, NO (nitric oxide), kinins, platelet-activating factor, endothelins and the four families of traditional eicosanoids - the leukotrienes and three types of prostanoids i.e. prostaglandins, prostacyclins, and thromboxanes. Several other natural occurring molecules are sometimes called eicos-anoid, including the hepoxilins, resolvins, isofurans, isoprostanes, lipoxins, epoxyeicosatrienoic acids (EETs) and some endocannabinoids. However, not... 

Angioedema may be precipitated by histamine release but appears to be maintained by peptide kinins that are not affected by antihistaminic agents. For atopic dermatitis, antihistaminic drugs such as diphenhydramine are used mostly for their sedative side effect, which reduces awareness of itching. 

Kinins produce marked vasodilation in several vascular beds, including the heart, kidney, intestine, skeletal muscle, and liver. In this respect, kinins are approximately 10 times more potent on a molar basis than histamine. The vasodilation may result from a direct inhibitory effect of kinins on arteriolar smooth muscle or may be mediated by the release of nitric oxide or vasodilator prostaglandins such as PGE2 and PGI2. In contrast, the predominant effect of kinins on veins is contraction again, this may result from direct stimulation of... 

Kinins, neuropeptides, and histamine are also released at the site of tissue injury, as are complement components, cytokines, and other products of leukocytes and platelets. Stimulation of the neutrophil membranes produces oxygen-derived free radicals. Superoxide anion is formed by the reduction of molecular oxygen, which may stimulate the production of other reactive molecules such as hydrogen peroxide and hydroxyl radicals. The interaction of these substances with arachidonic acid results in the generation of chemotactic substances, thus perpetuating the inflammatory process. 

Kinins, neuropeptides, and histamine are also released at the site of tissue injury, as are complement components, cytokines, and other products of leukocytes and platelets. Stimulation of the neutrophil... 

Bradykinin and related kinin peptides are produced by leucocytes and act via Gaq to elevate cytosolic Ca2+ and promote nitric oxide (NO) synthesis, smooth muscle contraction, capillary permeability, inflammation and histamine release from mast cells. 

In fact, a medley of substances (autacoids), kinins, prostaglandins, leukotrienes, histamine, endorphins, serotonin, vasopressin, has been implicated. In endotoxic shock, the toxin also induces synthesis of nitric oxide, the endogenous vasodilator, in several types of cells other than the endothelial cells which are normally its main source. 

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