Neural control of lower airway vasculature. Involvement of classical transmitters and neuropeptides

Abstract

1. SP- and CGRP-IR fibres of presumably sensory origin were abundantly located around the vasculature and glands in the laryngotracheal and bronchial mucosae of the pig. A sparse presence of CGRP- and SP-IR nerves in the tracheobronchial smooth muscle layer as well as an atropine-sensitive bronchoconstrictor response to electrical field stimulation suggested that neuropeptides locally released from sensory nerves may be related to vascular or exocrine gland function rather than to bronchial smooth muscle control. In the tracheal mucosa, many VIP-positive perivascular nerve fibres, likely to be of local parasympathetic origin, were present, whereas very few or no such fibres were found in the bronchial mucosa or in the pulmonary vascular bed. A dense innervation of the tracheobronchial and pulmonary vasculature by NPY/DBH-containing perivascular fibres suggested that the sympathetic control of these vascular beds may not only involve NA as transmitter. 2. Mainly sensory axon reflex mechanisms occurred upon systemic capsaicin injection in the pig after pretreatment with a combination of autonomic blocking agents, as revealed by plasma elevations of CGRP- and NKA-LI but not NPY-LI or catecholamines. Repeated capsaicin injections, in the presence of autonomic blocking agents, caused a marked reduction in the elevation of plasma CGRP- and NKA-LI with a clear-cut fall in the bronchial vascular response, suggesting development of tachyphylaxis for local sensory mechanisms. 3. Vasodilatory vagal mechanisms involved different neurotransmitters in the lower airway vasculature of the pig. Thus, local blood flow in the laryngo-tracheal circulation was regulated by cholinergic and non-cholinergic parasympathetic mechanisms and a small capsaicin-sensitive sensory component, while the vagal control of the bronchial circulation seemed to mainly involve capsaicin-sensitive sensory nerves. VIP and ACh were more potent as vasodilators in the laryngo-tracheal compared to the bronchial circulation. Exogenous SP was the most potent vasodilator peptide in the lower airway mucosa. SP and CGRP mimicked capsaicin-induced vasodilatation in the laryngo-tracheal and bronchial circulations. In the pulmonary circulation, vagal activation evoked atropine-sensitive vasoconstriction, probably due to sympathetic reflexes, but not vasodilatation. 4. Both NA and NPY had potent vasoconstrictor effects in the airway mucosa.(ABSTRACT TRUNCATED AT 400 WORDS)