Irritative and protective activity of mild irritants in rat stomach

Exposure of the stomach for 30 min to acidified sodium taurocholate (TC) (1–20 mM) or sodium salicylate (SA) (10–80 mM) caused a reduction of transmucosal PD and an increase of luminal pH in anesthetized rats, in a concentration-related manner. Acidified aspirin (ASA) (10–80 mM) reduced PD in the same manner, without significant effect on pH. Histologically, these agents similarly produced damage to the surface cells. After a 30-min exposure to either 20 mM TC or 40 mM SA, acid secretion ceased and bicarbonate (0.5–1 mol/10 min) appeared in the lumen, whereas acid secretion persisted in the stomach exposed to 40 mM ASA. However, under cimetidine infusion (8 mg/kg/hr) these agents produced similar degrees of luminal alkalinization (1 mol/10 min). Pretreatment with indomethacin (5 mg/kg, subcutaneously) significantly inhibited the increase of pH seen after exposure to 20 mM TC, but had no effect on the increase of pH caused by 40 mM SA. Concurrent administration of 16,16-dmPGE₂ (3 g/kg, subcutaneously) significantly antagonized the effect of indomethacin in the stomach exposed to 20 mM TC and even increased the pH in the stomach exposed to 40 mM ASA. After a 3-hr exposure to these agents, there was macroscopically apparent damage only in the stomach exposed to ASA, although the PD was similarly reduced in response to either agent. The levels of PGE₂ in the corpus mucosa were significantly increased in stomachs exposed to 20 mM TC and 40 mM SA, but decreased in those exposed to 40 mM ASA. Pretreatment with indomethacin significantly blocked the increased formation of PGE₂ caused by TC and SA. These results suggest that mucosal damaging agents such as TC and SA reduce the PD (surface cell injury) and act as mild irritants to induce gastric alkaline response and adaptive mucosal protection, unless, as in the case of ASA, they have an inhibitory effect on prostaglandin synthesis.     

Occupational airways diseases from chronic low-level exposures to irritants

Short-term, high-level exposures to dusts, gases, mists, fumes, and smoke that are irritating to the respiratory tract are capable of inducing asthma, the so-called reactive airways dysfunction syndrome. Such exposures, however, do not occur frequently; chronic or recurrent exposures to lower levels of irritants are much more common. This article reviews the evidence that supports the concept that low-level exposures to respiratory tract irritants can contribute to the development of chronic obstructive pulmonary disease and asthma.     

The effects of air pollutants and irritants on the upper airway

The nose and upper airway play a sentinel role in the respiratory tract, alerting an individual to the qualities of the inspired atmosphere. The upper airway also clears contaminants from the inspired airstream and physically conditions inspired air before its entry into the lower respiratory tract. Given these anatomical and functional considerations, the nose may be the initial-or even prime-target of air pollutants. This article reviews the functional anatomy of the upper airway in humans, its vulnerabilities to various classes of air contaminants, and the relationship between chemical irritation and allergic inflammation in the upper airway.     

Sensitivity of vagal afferent endings to chemical irritants in the rat lung

This study was carried out to investigate the relationship between the conduction velocity of the vagal afferents arising from the rat lungs and their sensitivities to capsaicin, other chemical irritants, and lung inflation. We recorded single-unit activities of vagal pulmonary afferents (n = 205) in anesthetized, open-chest rats, and distinguished C fibers (conduction velocity < 2 m/sec) from myelinated afferents; the latter group was further classified into rapidly adapting pulmonary receptors (RARs) and slowly adapting pulmonary stretch receptors (SARs) on the basis of their adaptation indexes to lung inflation. Right-atrial injection of capsaicin (1 microg/kg) evoked an abrupt and intense stimulatory effect in 88.9% (64/72) of the pulmonary C fibers tested, but only a mild stimulation in 6.3% (3/48) of the RARs and none of the SARs. Other inhaled and injected chemical stimulants (e.g., cigarette smoke, lactic acid) activated 68.9% (42/61) of the pulmonary C fibers. The same chemical irritants exerted a mild stimulatory effect in only 14.5% (8/55) of the RARs; this subgroup of RARs exhibited a low or no baseline activity, and half of them were located near the hilum. Chemical stimulants had little or no effect on SARs. The response of pulmonary C fibers to lung inflation (tracheal pressure = 30 cm H2O) was not only extremely weak, but also showed a longer onset latency and an irregular pattern. In a sharp contrast, lung inflation evoked rapid and vigorous discharges in both RARs and SARs. In conclusion, C fibers are the primary type of chemosensitive vagal pulmonary afferents in rat lungs.