as been recognized for some time that PGD2 has the potential to mediate the pathological blood flow AEB 071 site changes observed in allergic diseases. In the case of allergic rhinitis, engorgement of the vasculature in the nose contributes to congestion, a troublesome symptom, which is largely resistant to the action of H1 antagonists. The mechanisms of the vascular changes in the mucosa of patients allergic rhinitis is complex but is thought to involve the direct actions of mediators on both the vasculature and neuronal reflexes. Blood flow changes contribute to the swelling of the nasal mucosa causing congestion and enhanced leakage of plasma protein, which contributes to nasal secretions. The importance of blood flow changes to the signs and symptoms of rhinitis is evident based on the effectiveness of vasoconstrictors such as pseudoephedrine to reduce `stuffiness’. In human volunteers intravenous administration 
of PGD2 has been shown to produce nasal congestion associated with intense facial flushing but interestingly, no overt effects on systemic blood pressure or lung function. Congestion has also been observed after insufflation of PGD2 in human subjects and it is more effective in this respect than either histamine or bradykinin 153 S191S199 S194 Role of DP1 and CRTH2 in allergic inflammation R Pettipher 1990). The ability of PGD2 to induce nasal air flow resistance is blocked by the vasoconstrictor oxymetazoline highlighting the importance of a vascular event in mediating this response. Production of PGD2 in response to allergen in pigs has been proposed to mediate a long-lasting component of airway vasodilatation resistant to antihistamines. This conclusion is based on the ability of PGD2 to mimic the long-lasting airways vasodilatation induced by allergen and the inhibitory effect of the cyclooxygenase inhibitor diclofenac on allergeninduced blood flow changes. The vasoactive effect of PGD2 appears to be more marked in the nose than the lower airways and so be more relevant to allergic rhinitis than asthma. The availability of selective DP1 agonists and antagonists have shown that vasorelaxation of vascular smooth muscle in response to PGD2 is DP1-mediated and the hypotensive effect of PGD2 is inhibited by BW A868C which suggests that the vascular effects described above are likely to be mediated by PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19803812 DP1. Indeed, the selective DP1 agonist BW245C-induced headache, nasal stuffiness and facial flushing when infused into human volunteers. Most recently it has been shown that increased nasal airway resistance induced by intranasal instillation of PGD2 in conscious sheep is completely inhibited by a selective DP1 antagonist. While there are no reports on the effects of selective DP1 antagonists on vascular engorgement or congestion in clinical allergy it is of interest that the DP1 antagonist MK0524 has been reported to reduce facial flushing in human volunteers administered niacin. Niacininduced flushing is mediated by the production of endogenous PGD2 by cells in the skin, probably Langerhans’ cells which then acts on DP1 to mediate increased blood flow. The relationship between activation of DP1 and nasal blockage has been explored in sensitized guinea pigs where it was found that the selective DP1 antagonist S-5751 inhibited the early phase increase in nasal pressure in response to allergen while the H1 antagonist terfenadine was without effect. It seems likely therefore that at sites of mast activation PGD2 is produced and this mediator co
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