Mechanisms of cigarette smoke-induced stimulation of rapidly adapting receptors in canine lungs.
The stimulation of rapidly adapting receptors (RARs) in the lungs evoked by cigarette smoke consists of an initial and either a type I or a type II delayed response (Kou and Lee, J. Appl. Physiol. 68: 1203, 1990). In the type I response, receptor activity increased during expirations and exhibited a prominent cardiac modulation, whereas in the type II response, receptor discharge reached its peak during inspiration at peak transpulmonary pressure. To investigate the mechanisms of this stimulation, we recorded the vagal afferent activity arising from 39 RARs and delivered a single breath (120 ml) of cigarette smoke in 15 anesthetized, open-chest and artificially ventilated dogs. Studies were repeated after a pretreatment with aerosolized hexamethonium (3-8 breaths, 10%), aerosolized isoproterenol (12-15 breaths, 2%), or after the cardiac impact on the lung had been minimized by elevating the apex of the heart. The initial response of RARs was totally abolished by hexamethonium but was not affected by isoproterenol. The increase of total lung resistance induced by cigarette smoke and the concomitant type II delayed response of RARs were both abolished by isoproterenol. The type I delayed response of RARs was eliminated or largely attenuated after the apex of the heart had been elevated. Based upon these results, we conclude that a direct effect of nicotine on these receptors may be responsible for the immediate stimulation while the systemic effects of absorbed nicotine may play a part in evoking the delayed stimulation.
Department of Physiology and Biophysics, University of Kentucky Medical Center, Lexington.
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Kou
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Lee
D000222:Adaptation, Physiological; D000704:Analysis of Variance; D000818:Animals; D004285:Dogs; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D012907:Smoking / Q000503:physiopathology*
D006584:Hexamethonium Compounds; D011956:Receptors, Cell Surface; D018738:Hexamethonium; D009538:Nicotine; D007545:Isoproterenol