Modulation of the release and activity of neuropeptides in the microcirculation.
Electrical stimulation of the sensory saphenous nerve leads to neurogenic edema formation in the innervated area of the paw of the anesthetized rat. Evidence suggests that the edema formation is the result of increased microvascular permeability mediated via neurokinin NK1 receptors and increased blood flow mediated via calcitonin gene related peptide CGRP1 receptors. Results indicate that selective receptor antagonists will only inhibit the response mediated by the specific receptor they antagonise. In the case of neurogenic inflammation, where it is common for more than one biologically active neuropeptide to be released concomitantly, it may be more sensible to develop agents that inhibit neuropeptide release. The effects of some agents suggested to affect neurogenic responses are presented. The anti-inflammatory steroid dexamethasone (1 mg/kg subcutaneously, -4 h) significantly (p < 0.01) inhibited edema formation, but the mechanism of action is likely to be related to the general anti-edema effect of dexamethasone. In contrast the anti-asthma agent nedocromil sodium (up to 10 mg/kg intravenously, -15 min) and the histamine H3 agonist (R)-alpha-methyl histamine (1-10 mg/kg intravenously, -5 min) both failed to inhibit saphenous nerve induced edema formation, despite positive results in other sensory nerve systems. The results are discussed in the context of evidence obtained using other agents in skin.
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Pharmacology Group, King's College, London, United Kingdom.
Newbold
P
P
Kajekar
R
R
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004487:Edema / Q000209:etiology / Q000517:prevention & control*; D004558:Electric Stimulation; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D017835:Nedocromil / Q000494:pharmacology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D008761:Methylhistamines; D009479:Neuropeptides; D017835:Nedocromil; C069357:alpha-methylhistamine; D003907:Dexamethasone