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

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.Onmol kg-, 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 doserelated 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. IntroductionElectrical stimulation of the cervical vagus nerves in rat and guinea-pig induces a number of physiological responses including vasodilatation and increased permeability of the microvasculature of the trachea to macromolecules (Lundberg & Saria, 1982;Lundberg et al., 1983). Both responses are preserved in the presence of atropine, hexamethonium or antihistaminic drugs, but are absent in animals pretreated with capsaicin. Capsaicin is the major pungent principle of hot peppers of the plant genus Capsicum and has been shown to deplete primary afferent C-fibres of stored neuropeptides (Buck & Burks, 1986). Capsaicin itself causes a depolarization of afferent Cfibres which induces local effects including vasodilatation and plasma extravasation in guinea-' Author for correspondence.pigs (Lundberg et al., 1984a). The physiological responses may, therefore, be due to release of neuropeptides localized to capsaicin-sensitive nerves. For example, the tachykinin substance P (SP) has been localized to sensory nerves in the airways of several species, including man (Lundberg et al., 1984b). SP and two newer members of the tachykinin family, neurokinin A (NKA) and neurokinin B (NKB) have been shown to increase vascular permeability in guinea-pig trachea (Lundberg et al., 1985) although, of the two neurokinins, only NKA has been localized to capsaisin-sensitive nerves in the guinea-pig (Hua...

Bradykinin‐induced plasma exudation in guinea‐pig airways: involvement of platelet activating factor

“…Cholinergic mechanisms contribute little or nothing to airway plasma leakage whereas NANC neural mechanisms potently induce airway exudation in rodents . This 'neurogenic' plasma exudation can be blocked in a number of ways including the use of anaesthetics such as Hypnorm which contain opiates (Belvisi et al, 1988). Animals anaesthetized with Hypnorm should exhibit reduced leakage in response to bradykinin compared with those anaesthetized with urethane, a nonopioid containing anaesthetic, when the anti-leakage effects of urethane-induced release of endogenous catecholamines (Spriggs, 1965) are blocked by adrenoceptor antagonists (Boschetto et al, 1988).…”

“…We have shown previously (Belvisi et al, 1988) that leakage due to the non-adrenergic, non-cholinergic (NANC) component of vagus nerve stimulation is significantly attenuated with diazepam-Hypnorm: leakage under urethane anaesthesia should be relatively greater. To prevent urethane-induced release of endogenous catecholamines reducing the magnitude of leakage (Boschetto et al, 1988), phentolamine (2.5mg kg-1) and propranolol (1 mgkg-1) were given i.v.…”

Avaliação espectrofotométrica do azul de Evans na reação inflamatória da córnea: estudo experimental em coelhos

“…Há outros corantes, além do azul de Evans, que se ligam à albumina, como o azul Celeste de Niágara, o azul Celeste de Pontamina 6BX e o azul de Tripan (2,(10)(11)(12)(13)(14)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) . O azul de Evans é um corante capaz de ser mensurável por meio de espectrofotometria (11)(12) .…”

Differential effects of phosphoramidon on neurokinin A‐ and substance P‐induced airflow obstruction and airway microvascular leakage in guinea‐pig

“…These tachykinins can cause several pathological effects in the airways, including airway smooth muscle contraction, mucus secretion and increased microvascular permeability (Nilsson et al, 1977;Andersson & Persson, 1977;Saria et al, 1983;Hua et al, 1984;Coles et al, 1984;Rogers et al, 1988;Lotvall et al, 1990a). It has also been shown that inhaled NKA, but not SP, causes airway narrowing in asthmatic patients, but not in non-asthmatics (Joos et al, 1986;Fuller et al, 1987).…”