Airways vasodilatation in the immediate allergic reaction. Involvement of inflammatory mediators and sensory nerves.
1. Systemic capsaicin treatment of the pig depletes the content of sensory neuropeptides (CGRP and tachykinins) in the airways mucosa and skin, without affecting sympathetic and parasympathetic nerves containing NPY and VIP, or the presence and appearance of inflammatory cells including mast cells. Acute capsaicin exposure caused release of sensory neuropeptides and catecholamines, and marked vasodilation in the airways and skin, without signs of plasma protein extravasation or bronchoconstriction. Capsaicin pretreatment effectively desensitizes against local challenges with capsaicin in the airways and skin, as revealed by the absence of vasodilatory responses 2 days later. 2. Cigarette smoke exposure induces marked vasodilatation, lasting for about 5 min in both the upper and lower airways, which seems not to be primarily caused by particulate matter or nicotine in the smoke. Except for a minor capsaicin-sensitive component in the nasal circulation, these responses probably do not involve neural activation, mast cell degranulation or prostaglandin formation. Rather, it is concluded that vapour phase components act on the vessels via unknown mechanisms. 3. Sensitization of pigs with s.c. injections of ascaris antigen was successful, resulting in typical wheal and flare reactions in the skin and bronchoconstriction after local challenge with antigen. The reactivity to ascaris is probably mediated by antibodies of the IgE isotype. 4. Histamine-containing mast cells and sensory neuropeptide-containing nerve fibers show close morphological association around blood vessels in the pig skin. Both alcian blue-positive mast cells and capsaicin-sensitive sensory nerves are present close to the pig airways epithelium. Sensory neuropeptide-containing nerves are also abundant around airways mucosal blood vessels, whereas the bronchial smooth muscle is sparsely innervated. 5. Allergen and histamine injections in the skin caused similar responses consisting of flare and protein extravasation. Allergen challenge in the airways induces marked vasodilatation lasting for 60-90 min in the pig bronchial and nasal circulations. Histamine seems to be important in the early phase (0-20 min) of these responses in the airways, while cyclooxygenase products (possibly PGD2) may be responsible for the longlasting component. A cyclo-oxygenase product is presumably also released from the lung into the circulation after bronchial allergen challenge and thereby induces a delayed, long-lasting nasal vasodilatation. Histamine may be the main bronchoconstrictor agent released in the immediate allergic reaction of the pig. 6. The flare, but not the protein extravasation reaction, to allergen and histamine injections in the skin, was inhibited by capsaicin pretreatment.(ABSTRACT TRUNCATED AT 400 WORDS)
Alving
K
K
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D008407:Mast Cells / Q000276:immunology; D009475:Neurons, Afferent; D012137:Respiratory System / Q000098:blood supply* / Q000276:immunology / Q000294:innervation; D012867:Skin / Q000098:blood supply / Q000276:immunology; D013552:Swine; D014664:Vasodilation
D002211:Capsaicin