Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs

Abstract

tients with chronic bronchial asthma show a depressed ventilatory response to hypoxia (DVH), but the underlying mechanism remains unclear. We tested whether DVH existed in ovalbumin (Ova)-treated guinea pigs, an established animal model of asthma. Twelve guinea pigs were exposed to Ova (1% in saline) or saline aerosol (control) for 5 min, 5 days/wk, for 2 wk. After completing aerosol exposure, the animals were anesthetized and exposed to systemic hypoxia. Ova treatment had no effects on animal body weight, baseline cardiorespiratory variables, or arterial blood O 2 and CO2 tensions, but it attenuated the ventilatory response to hypoxia (10 breaths of pure N 2) by 65% (P Ͻ 0.05). When the animals were subjected to intracarotid injections of sodium cyanide (20 g) and doxapram (2 mg) to selectively stimulate carotid chemoreceptors, the ventilatory responses were reduced by 50% (P Ͻ 0.05) and 74% (P Ͻ 0.05), respectively. In contrast, Ova exposure failed to affect the ventilatory response to CO 2 (7% CO2-21% O2-balance N2 for 5 min; P Ͼ 0.05). Furthermore, the apneic response evoked by stimulating bronchopulmonary C fibers (PCFs) with right atrial injection of capsaicin (5 g) was markedly increased in the Ova-sensitized group (5.02 Ϯ 1.56 s), compared with the control group (1.82 Ϯ 0.45 s; P Ͻ 0.05). These results suggest that Ova sensitization induces a DVH in guinea pigs, which probably results from an attenuation of the carotid chemoreceptor-mediated ventilatory excitation and an enhancement of the PCF-mediated ventilatory inhibition. carotid body; bronchopulmonary C fibers; hypoxia; capsaicin; inflammation RESPIRATORY FAILURE FROM ASTHMA is a common clinical symptom and a primary cause of high mortality. A study through a period of 7 yr indicated that 68% of asthmatic patients had two or more episodes of respiratory failure that led to an ϳ10% death rate (30). Ventilatory arrest in the near-fatal nature of the exacerbations is dominant compared with cardiac arrest (26). It is generally recognized that patients with chronic bronchial asthma have a depressed ventilatory response to hypoxia (DVH) that may contribute to the respiratory failure (4, 11, 14 -16, 21, 33, 38), although an absence (27) of DVH or an increase of ventilatory response to hypoxia (20) was also reported. Hudgel and Weil (14,15) first reported a severe DVH in asthmatic individuals in 1974. Subsequent studies confirmed this observation and further indicated that the amplitude of minute ventilation (V E) in response to progressive isocapnic hypoxia was significantly attenuated in both young and adult patients compared with age-matched normal subjects (4,11,16,21,33,38). A severely diminished hypoxic perception was also found in asthmatic patients; a typical example is that the patients who had asthma displayed cyanosis but had no dyspnea at all (21). This blunted hypoxic perception could impair the behavioral control of breathing and worsen hypoxemia by reducing ventilatory augmentation. To date, the pathophysiological mechanisms underlying DVH i...

Ovalbumin sensitizes vagal pulmonary C-fiber afferents in Brown Norway rats

“…3-5). Recent investigations reported that OVA sensitization significantly enhanced PCF activities (6) and the apneic response to capsaicin (57). The results of the present study also provide the direct electrophysiological evidence demonstrating the OVA sensitization induced PCF hypersensitivity.…”

Respiratory syncytial virus infection in anesthetized weanling rather than adult rats prolongs the apneic responses to right atrial injection of capsaicin

“…We found that the latency to evoke the initial apnea was ϳ1.7 s in weanling and adult rats, similar to that previously reported in postnatal and adult anesthetized rats and cats (20,33,34,36,37). Interestingly, in the present study, RSV infection prolonged the initial apneic duration by 40%, which is much smaller than the CAP impacts on the following apneas (the longest apneic duration was prolonged by 650% and the apneic episodes by 139%).…”

Anti-Anaphylactic Activity of Isoquercitrin (Quercetin-3-O-β-d-Glucose) in the Cardiovascular System of Animals

“…When the antigen OVA was injected into pre-sensitized, isolated guinea pig hearts, immediate and dramatic cardiac functional changes occurred [18]. Namely, the coronary flow diminished markedly and the contractile force increased initially (in about 2 min post-OVA challenge in this…”