Effects and interactions of sensory neuropeptides on airway microvascular leakage in guinea-pigs

Open Access
Publisher Website
Google Scholar
Abstract
1 We have studied the effect of the sensory neuropeptides substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) on microvascular permeability in guinea-pig airways in vivo and investigated whether CGRP would potentiate the effect of SP. We used the extravasation of intravenously-injected Evans blue dye as an index of permeability. 2 The tachykinins SP, NKA and NKB (0.025–5.0 nmol kg−1, i.v.) significantly (P < 0.05) increased extravasation of dye in a dose-related manner and with a similar pattern of distribution; they were most potent in the trachea and main bronchi, less potent in the larynx and intrapulmonary airways, and had little significant effect in the bladder. 3 SP was significantly more potent in causing extravasation of dye than NKA or NKB with ED50 values (nmol kg−1) in the range 0.04–0.1, depending on the airway level, compared with values in the range 0.3–0.7 for the neurokinins. 4 CGRP (0.0025–2.5 nmol kg−1, i.v.) had no significant effect on microvascular permeability and did not potentiate SP-induced extravasation of dye. 5 Each neuropeptide decreased mean arterial blood pressure, indicating vasodilatation, in a dose-related manner. Co-injection of CGRP and SP produced additive decreases in arterial pressure. 6 We conclude that, in guinea-pig airways, tachykinins increase microvascular permeability via tachykinin receptors of the NK-1 sub-type (indicated by an order of potency of SP > NKA = NKB) on endothelial cells. The response appears to be related to mechanisms in addition to vasodilatation. The relevance of the responses to the tachykinins in asthma is discussed.