Cigarette Smoke In Guinea Pigs Research Articles

Cigarette smoke increases mucosal permeability in guinea pig trachea via tachykinin NK 2 receptor activation

We investigated whether exposure to cigarette smoke increases the mucosal permeability in guinea pig trachea and if this effect could be mediated by tachykinin NK 2 receptor activation. Guinea pigs were exposed to either three different doses of cigarette smoke or room air. Mucosal permeability was measured by monitoring the rate of appearance in the circulation of horseradish peroxidase (HRP) that had been instilled into the isolated tracheal segment. Exposure to 20 and 30 puffs but not 10 puffs of cigarette smoke increased the tracheal mucosal permeability. Pretreatment with the tachykinin NK 2 receptor antagonist SR48,968 [( S)- N-methyl- N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide] completely inhibited the increase in the permeability of the tracheal mucosa induced by exposure to cigarette smoke, whereas the tachykinin NK 1 receptor antagonist SSR240,600 [( R)-2-(1-{2-[4-{2-[3,5-bis(trifluoromethyl)phenyl]acetyl}-2-(3,4-dichlorophenyl)-2-morpholinyl]ethyl}-4-piperidinyl)-2-methylpropanamide] and the tachykinin NK 3 receptor antagonist SR142,801 [( S)-( N)-(1-[3-(1-benzoyl-3(3,4-dichlorophenyl)piperidine-3-yl)propyl]-4-phenylpiperidin-4-yl)- N-methyl-acetamide] had no effect. It is concluded that endogenous tachykinins via NK 2 receptor activation mediate the increase in the permeability of the tracheal mucosa induced by exposure to cigarette smoke in guinea pigs.

A model for quantitative cigarette smoking and response of airways to cigarette smoke in guinea pigs

To establish an animal model for quantitative cigarette smoking and to determine the acute response of airways to cigarette smoke in guinea pigs. The device for inhaling quantitative cigarette smoking was made, which was double pass and single-direction with the minimum dead space. The changes of airway resistance(R(L))and dynamic lung compliance(Cdyn) in guinea pigs exposed to compound air consisting of 75% cigarette smoke and 25% oxygen were observed. Exudation of Evans blue in pulmonary vessels was also determined after consecutive inhalation of 60 ml smoke. The R(L) increased from the baseline of (0.21+/-0.05) cmH(2)O x ml(-1) x s to (0.37+/-0.13) cmH(2)O x ml(-1) x s after 10 consecutive breaths of cigarette smoke exposure(P<0.01). The Cdyn decreased to (61+/-19)% of baseline at the ninth to eleventh breaths (P<0.01). The exudations of Evans blue significantly increased in all measured parts of the airways such as lower trachea, main bronchi, proximal intrapulmonary airways and distal intrapulmonary airways (P<0.01). The model established in this study is useful for measuring the acute responses of airways induced by cigarette smoke in guinea pigs. Acute inhalation of cigarette smoke decreases dynamic lung compliance, increases airway resistance and vascular permeability of pulmonary vessels in guinea pigs.

Airway hyperresponsiveness induced by chronic exposure to cigarette smoke in guinea pigs: role of tachykinins.

This study was carried out to determine whether tachykinins released from lung C-fiber afferents play a part in the bronchial hyperreactivity induced in guinea pigs by chronic exposure to cigarette smoke (CS). Two matching groups of young guinea pigs were exposed to either mainstream CS (CS group) or air (control group) for 20 min twice daily for 14-17 days. There was no difference in the baseline total pulmonary resistance (RL) between the two groups, but the baseline dynamic lung compliance was reduced ( approximately 19%) in CS animals. The responses of RL to intravenous injections of ACh, neurokinin (NK) A, and capsaicin were all markedly increased in CS animals; for example, ACh at the same dose of 5.06 microg/kg increased RL by 207% in the control group and by 697% (n = 8; P < 0. 001) in the CS group. The increased responsiveness was accompanied by significant increases in the numbers of neutrophils, eosinophils, and macrophages in the bronchoalveolar lavage fluid in CS animals. Pretreatment with SR-48968 and CP-99994, antagonists of NK(1) and NK(2) receptors, respectively, did not alter the response of RL to ACh in control animals, but it abolished the elevated bronchoconstrictive response in the CS animals. Furthermore, the immunoreactivities of substance P and calcitonin gene-related peptide in the bronchoalveolar lavage fluid collected after capsaicin challenge were significantly increased in CS animals. These results show that chronic exposure to CS induced airway mucosal inflammation accompanied by bronchial hyperreactivity in guinea pigs and that the tachykininergic mechanism plays an important role in this augmented responsiveness.

Role of adrenergic nervous system in cigarette smoke-induced bronchoconstriction in guinea pigs

The goal of this study was to clarify the role of the adrenergic nervous system in bronchoconstriction induced by exposure to cigarette smoke in guinea pigs. Artificially ventilated animals were exposed to 160 puffs of smoke for 8 min. Bronchoconstriction was assessed as a percentage of the baseline total pulmonary resistance ( R L). The effects of pretreatment with phentolamine (0.1 mg/kg, i.v.), propranolol (1 mg/kg, i.v.), and/or atropine (1 mg/kg, i.v.) were evaluated. Exposure to cigarette smoke caused significant bronchoconstriction. Phentolamine, an α-adrenoceptor antagonist, significantly inhibited cigarette smoke-induced bronchoconstriction, while propranolol, a β-adrenoceptor antagonist, significantly enhanced it. Combined use of these compounds further enhanced the bronchoconstriction. All of modulations of the bronchoconstriction by adrenoceptor antagonists were completely abolished by pretreatment with atropine. Phentolamine and/or propranolol had no effect on the bronchoconstriction induced by inhaled acetylcholine. Pretreatment with yohimbine (0.5 mg/kg, i.v.), a selective α 2-adrenoceptor antagonist, showed modulatory effects similar to those of phentolamine on cigarette smoke-induced bronchoconstriction. These results suggest that cigarette smoke-induced bronchoconstriction is regulated by the prejunctional modulation of the cholinergic system via α- and β-adrenoceptors. This mechanism may be modulated by the autoregulation of adrenergic nerves via the α 2-autoreceptor.

Role of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs.

Acute exposure to ozone (O3) induces airway hyperresponsiveness to various inhaled bronchoactive substances. Inhalation of cigarette smoke, a common inhaled irritant in humans, is known to evoke a transient bronchoconstrictive effect. To examine whether O3 increases airway responsiveness to cigarette smoke, effects of smoke inhalation challenge on total pulmonary resistance (RL) and dynamic lung compliance (Cdyn) were compared before and after exposure to O3 (1.5 ppm, 1 h) in anesthetized guinea pigs. Before O3 exposure, inhalation of two breaths of cigarette smoke (7 ml) at a low concentration (33%) induced a mild and reproducible bronchoconstriction that slowly developed and reached its peak (DeltaRL = 67 +/- 19%, DeltaCdyn = -29 +/- 6%) after a delay of >1 min. After exposure to O3 the same cigarette smoke inhalation challenge evoked an intense bronchoconstriction that occurred more rapidly, reaching its peak (DeltaRL = 620 +/- 224%, DeltaCdyn = -35 +/- 7%) within 20 s, and was sustained for >2 min. By contrast, sham exposure to room air did not alter the bronchomotor response to cigarette smoke challenge. Pretreatment with CP-99994 and SR-48968, the selective antagonists of neurokinin type 1 and 2 receptors, respectively, completely blocked the enhanced responses of RL and Cdyn to cigarette smoke challenge induced by O3. These results show that O3 exposure induces airway hyperresponsiveness to inhaled cigarette smoke and that the enhanced responses result primarily from the bronchoconstrictive effect of endogenous tachykinins.

Role of thromboxane-A2 and cholinergic mechanisms in bronchoconstriction induced by cigarette smoke in guinea-pigs.

Acute exposure to cigarette smoke provokes bronchoconstriction and increases the concentration of thromboxane (Tx) A2 in bronchoalveolar lavage (BAL) fluid. The purpose of this study was to investigate the role of TxA2 and cholinergic mechanisms in the airway response induced by exposure to cigarette smoke in guinea-pigs. Anaesthetized animals were exposed to 200 puffs of smoke for 10 min. The amount of Evans blue dye extravasated into the bronchial tissue was then measured BAL was performed to determine cell counts and the concentration of TxB2, a stable metabolite of TxA2. The effects of pretreatment with a Tx synthase inhibitor, OKY-046 (10 mg.kg-1), and/or atropine (1 mg.kg-1) were evaluated. Exposure to cigarette smoke caused significant bronchoconstriction (284 +/- 33% of baseline pulmonary resistance (RL)) and plasma extravasation (30.0 +/- 3.8 vs 16.8 +/- 2.6 ng.mg-1 of sham control; main bronchi). OKY-046 or atropine significantly inhibited the bronchoconstriction to a similar extent, without affecting the plasma extravasation. Combined use of these compounds had no additive effect. The cigarette smoke caused significant increase in TxB2 (48 +/- 10 vs 14 +/- 1 pg.mL-1 of sham control) in BAL fluid, which was abolished by OKY-046 but not by atropine. The cellularity in BAL fluid was not different among groups. These results suggest that the bronchoconstriction induced by cigarette smoke is partially mediated by thromboxane A2, which is dependent on a cholinergic pathway.

Role of tachykinins in airway narrowing induced by cigarette smoke in guinea pigs

To investigate the mechanism of the airway narrowing induced by cigarette smoke, anaesthetized guinea pigs were exposed to 200 puffs of smoke for 10 min. Airway narrowing was assessed by monitoring the total pulmonary resistance ( R L). Plasma extravasation was determined by measuring the amount of Evans blue dye extravasated into the trachea and main bronchi. Exposure to cigarette smoke caused a marked airway narrowing and plasma extravasation. Pretreatment with the dual NK 1 and NK 2 receptor antagonist, FK224, abolished such airway narrowing and significantly inhibited the extravasation. While the NK 1 receptor antagonist, FK888, inhibited the extravasation, it had no effect on airway narrowing. Atropine partially inhibited airway narrowing without affecting extravasation. Results suggest that the airway narrowing induced by cigarette smoke is caused by tachykinins, and that a cholinergic pathway is involved. Thickening of the airway walls induced by NK 1 receptor-mediated extravasation may not be involved in such airway narrowing.

Cigarette smoke-induced bronchoconstriction and release of tachykinins in guinea pig lungs

Two series of experiments were carried out to determine whether the release of tachykinins is involved in the bronchoconstriction induced by inhalation of cigarette smoke in guinea pigs. In the first series, cigarette smoke consistently induced bronchoconstriction (ΔR l = + 203% and ΔCdyn = −46%) in anesthetized guinea pigs, and the response was only partially blocked by bilateral cervical vagotomy. However, the smoke-induced bronchial constriction was completely abolished in animals receiving a systemic capsaicin pretreatment to destroy the tachykinin-containing C-fiber afferents. In the second series, the bronchoconstrictive effect of cigarette smoke was increased by approx. three times in isolated perfused guinea pig lungs when phosphoramidon (3 × 10 −6 M) was added to the perfusate to prevent the degradation of tachykinins after their release. Moreover, the enhanced bronchomotor response to smoke was accompanied by an overflow of neurokinin A-like immunoreactivity (LI) and calcitonin gene-related peptide -LI in the pulmonary effluent. These studies showed that cigarette smoke triggers the release of tachykinins in the lungs, which plays an important role in the smoke-induced bronchoconstrictive effect in guinea pigs.

An experimental study on the influence of milk aspiration on bronchial reactivity to cigarette smoke in guinea pigs.

An experimental study on the influence of milk aspiration on bronchial reactivity to cigarette smoke in guinea pigs.