Microvascular leakage

Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma. The efficacy of corticosteroids is due to their ability to affect multiple inflammatory pathways, resulting in the suppression of inflammatory cell activation and function, prevention of microvascular leakage, decreased mucus production, and upregulation of P2-adrenergic receptors.10,18 Clinically, corticosteroids decrease airway inflammation, decrease AHR, decrease mucus production and secretion, and improve the response to P2-agonists.18 Corticosteroids for the treatment of asthma are available in inhaled, oral, and injectable dosage forms. 

K10. Klabunde, R. E., and Calvello, C., Inhibition of endotoxin-induced microvascular leakage by a platelet-activating factor antagonist and 5-lipoxygenase inhibitor. Shock 4, 368-372 (1995). 

Nishimura, H., Tokuyama, K., Inoue, Y., et al. (2001) Acute effects of prostaglandin D-2 to induce airflow obstruction and airway microvascular leakage in guinea pigs role of thromboxane A(2) receptors. Prostaglandins Other Lipid Medial. 66, 1-15. 

Fluticasone propionate inhibit microvascular leakage reduce need late reaction to allergen... 

Anaesthetised animal prejunctional (symp. nerves) Microvascular leakage increase Danko et al., 1994... 

Anaesthetised animal vagal afferent s Microvascular leakage inhibition Ichinose et al., 1990... 

Another interesting effect related to H3 receptors is its possible interference in the airway microvascular leakage (AML) induced by a variety of stimuli. Activation of H3 receptors inhibits NANC-induced leakage by reducing neuropeptides release from sensory fibers (Ichinose et al., 1990). Hence, H3 receptors may act as a safety device in asthmatic diseases to prevent, not only bronchoconstriction, but also increased airway permeability. On the other hand, it was also demonstrated that H3 receptor activation inhibits sympathetic tone, which, in turn, reduces antigen-induced AML (Danko et al., 1994). Therefore, the authors conclude that the blockade of H3 receptors may have therapeutic potential in inflammatory pulmonary... 

Danko, G., Hey, J.A., Egan, R.W., Kreutner, W., Chapman, R.W., 1994. Histamine H3 receptors inhibit sympathetic modulation of airway microvascular leakage in allergic guinea pigs. Eur. J. Pharmacol. 254, 283-286. 

Ichinose, M., Belvisi, M.G., Barnes, P.J., 1990. Histamine H3-receptor inhibit neurogenic microvascular leakage in airways. J. Appl. Physiol. 68, 21-25. 

Sakamoto, T., Barnes, P.J. and Chung, K.F. (1993). Effect of CP-96, 345, a non-peptide Nkl receptor antagonist, against substance P-, bradykinin- and allergpn-induced airway microvascular leakage and bronchoconstriction in the guinea-pig. Eur. J. Pharmacol. 231, 31-38. 

Advenier, C., Qian, Y., Koune, J.D., Molimard, M., Candenas, M.L. and Naline, E. (1992). Formoterol and salbutamol inhibit bradykinin and histamine-induced airway microvascular leakage in guinea-pig. Br. J. Pharmacol. 105, 792-798. 

Baluk, P. and McDonald, D.M. (1994). The jSi-adrenetgjc receptor agonist formoterol reduces microvascular leakage by inhibiting endothelial gap formation. Am. J. Physiol. 266, L461-L468. 

Barnes, P.J. (1993c). Effect of nedocromil sodium on microvascular leakage. J. Allergy Clin. Immunol. 92, 197-199. 

Evans, T.W., Rogers, D.F., Aursudkij, B., Chung, K.F. and Barnes, P.J. (1988b). Inflammatory mediators involved in antigen-induced airway microvascular leakage in guinea pigs. Am. Rev. Respir. Dis. 138, 395-399. 

Persson, C.G.A. and Erjefit, I. (1988). Non-neural and neural regulation of airway microvascular leakage of macromolecules. In Neural Regulation of the Airways in Health and Disease (eds M.A. Kaliner and P. Barnes), pp. 523-549. Marcel Dekker, New York. 

Some of these agents appear to have a very selective action at Hs-receptors, though there is some cross-talk with 5-HT3 receptors. None of these agents are used therapeutically yet, but suggested applications include inhibition of neurogenic microvascular leakage in airways, prevention of myocardial ischaemia, as anticonvulsants, appetite suppressants and cognition enhancers. 

Ito K, Sakamoto T, Hayashi Y, et al. 1996. Role of tachykinin and bradykinin receptors and mast cells in gaseous formaldehyde-induced airway microvascular leakage in rats. Eur J Pharmacol 307 291-298. Iversen OH. 1986. Formaldehyde and skin carcinogenesis. Environ Int 12 541-544. 

Neurokinin A (NKA) is a 10 amino acid peptide of the tachykinin family, with inflammatory and immune effects similar to SP. NKA is more potent than SP as a bronchoconstrictor, but less potent than SP in eliciting microvascular leakage and mucus secretion in lung tissues. This appears to be a function of the relative levels of expression by target cells of the GPCR NKl for SP and NK2 for NKA. The... 

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