Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs.
Patients 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 O2 and CO2 tensions, but it attenuated the ventilatory response to hypoxia (10 breaths of pure N2) by 65% (P < 0.05). When the animals were subjected to intracarotid injections of sodium cyanide (20 microg) and doxapram (2 mg) to selectively stimulate carotid chemoreceptors, the ventilatory responses were reduced by 50% (P < 0.05) and 74% (P < 0.05), respectively. In contrast, Ova exposure failed to affect the ventilatory response to CO2 (7% CO2-21% O2-balance N2 for 5 min; P > 0.05). Furthermore, the apneic response evoked by stimulating bronchopulmonary C fibers (PCFs) with right atrial injection of capsaicin (5 microg) was markedly increased in the Ova-sensitized group (5.02 +/- 1.56 s), compared with the control group (1.82 +/- 0.45 s; P < 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.
Xu
Fadi
F
Pathophysiology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, USA. fxu@lrri.org
Zhuang
Jianguo
J
Zhou
Tongrong
T
Lee
Lu-Yuan
LY
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D002211:Capsaicin / Q000494:pharmacology; D002245:Carbon Dioxide / Q000097:blood; D002344:Carotid Body / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004315:Doxapram / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006935:Hypercapnia / Q000276:immunology / Q000503:physiopathology; D000860:Hypoxia / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D009584:Nitrogen / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D015656:Respiratory Mechanics / Q000502:physiology*; D019141:Respiratory System Agents / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019141:Respiratory System Agents; D002245:Carbon Dioxide; D010047:Ovalbumin; D004315:Doxapram; D009584:Nitrogen; D012966:Sodium Cyanide; D002211:Capsaicin; D010100:Oxygen