| INTRODUCTIONInhalation of cigarette smoke could cause damage to the function of many viscera. Numerous smokers and enormous consumption of cigarettes consist in our country, whereas it is quite insufficient in the study about the airway responses to smoke and related diseases. In order to develop the basal research of diseases and therapy drugs related with cigarette smoke, we desire to establish an animal model for quantitive cigarette smoking in guinea pigs. Thus, the pulmonary responses after cigarette smoke exposure and the potential effects of certain drugs can be observed impersonally in this way.Cigarette smoke exposure stimulates the afferent sensory nerve C-fibers in the airways, which not only cause the release of acetylcholine (Ach) from the cholinergic nerves by vagal reflex, but also induced the release of tachykinins (SP, NKA) from the C-fiber endings via axon reflex. Furthermore, neurogenic inflammation in the airways including airway smooth muscle constriction, enhanced vascular permeability and mucus secretion can be triggered by the neurotransmittersreleased. In previous study, we have demonstrated that treatment with pethidine, a u-opioid receptor agonist inhibits the release of Ach and tachykinin from nerve endings via presynapic stimulation of the opioid receptors on airway cholinergic nerve and sensory nerve endings. It is well documented in certain related studies. In view of the increasing evidence of inhibition of opioids on airway neurogenic inflammation in separate bronchus preparations, we consider that in the whole animal, whether opioids can also inhibit excitatory responses of airway nerves and exhibit the inhibition on airway smooth muscle constriction, increased vascular permeability. Is it paradoxical with the description in the authoritative pharmacological monograph about elevatory effect of opioids in therapy dose on airway smooth muscle tone? We hypothesis that opioids used in small dose or low concentration cannot boost airway smooth muscle tone, but inhibit airway smooth muscle constriction and the enhancement of vascular permeability caused by stimulation of airway sensory nerves. If the hypothesis is correct, it might be significative in theory and in practice. Therefore, based on the model established, we try to determine the effect of low dose pethidine on airway smooth muscle constriction and increased vascular permeability induced by cigarette smoke in guinea pigs.AIMSThe present study aims to establish the animal model for quantitive cigarette smoking in guinea pigs and to observe the acute responses of airways to cigarette smoking. Further, we purpose to determine the effect of low dose pethidine on the cigarette smoke-induced airway smooth muscle constriction and the increased vascular permeability in guinea pigs.MATERRIALS AND METHODSThe device for quantitive cigarette smoking was established which demanded to permit guinea pigs to inhale fixed volume and certain concentration smoke automatically in the condition of normal atmospheric pressure and the minimum dead space. On the basis of the establishment of the smoking-device, three series of experiments were carried out.1. Measurement of pulmonary mechanical function after acute cigarette smoke exposureHartley guinea pigs were anesthetized. Then, 75 % cigarette smoke in the 60 ml smoke-container were delivered directly into the airways via the inspiratory line of smoking-device in 10 consecutive respirator cycles. Inhaled smoke was generated from the mid-portion of a lighted cigarette (4R1 series research cigarette of standard composition). The animals were exposed to air before the first inhalation of cigarette smoke as the control. A computer MedLab system recorded all physiological signals of transpulmonary pressure, respiratory flow and tidal volume continuously. Thereout total airway resistance and dynamic lung compliance were acquired. Self-control method was used to determine the variations of total airway resistance and dynamic lung compliance in this sec...
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