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

Abstract

Sensitization of vagal lung C fibers has been postulated to contribute to the development of asthma, but support for this notion is still lacking. We investigated the characteristics and function of pulmonary C fibers (PCFs) in ovalbumin (OVA)-sensitized Brown Norway rats, an established animal model of asthma. Rats were sensitized with intraperitoneal injection of OVA or were treated with saline (control). In study 1, with the use of open-chest and artificially ventilated rats, inhalation of 5% OVA aerosol evoked an augmented increase in total lung resistance in the OVA-sensitized rats, compared with the control rats. Bilateral vagotomy or subcutaneous pretreatment with a high-dose of capsaicin for blocking of C-fiber function equally attenuated this augmented total lung resistance response, suggesting the involvement of PCFs. In study 2, with the use of anesthetized, spontaneously breathing rats, right atrial injection of capsaicin (1 μg/kg; a PCF stimulant) evoked an augmented apneic response in the OVA-sensitized rats, compared with the control rats. In study 3, with the use of open-chest, paralyzed, and artificially ventilated rats, the afferent PCF responses to right atrial injection of capsaicin (0.5 and 1.0 μg/kg), phenylbiguanide (8 μg/kg; a PCF stimulant), or adenosine (0.2 mg/kg; a PCF stimulant) were enhanced in the OVA-sensitized rats, compared with the control rats. However, the baseline activities of PCFs and their afferent responses to mechanical stimulation by lung hyperinflation in the OVA-sensitized and control rats were comparable. Our results suggested that OVA-sensitized Brown Norway rats possess sensitized vagal PCFs, which may participate in the development of the airway hyperreactivity observed in these animals.