Potentiation of hypoxic ventilatory response by hyperoxia in the conscious rat: putative role of nitric oxide

In humans, the hypoxic ventilatory response(HVR) is augmented when preceded by a short hyperoxic exposure (Y. Honda, H. Tani, A. Masuda, T. Kobayashi, T. Nishino, H. Kimura, S. Masuyama, and T. Kuriyama. J. Appl.Physiol. 81: 1627-1632, 1996). To examine whetherneuronal nitric oxide synthase (nNOS) is involved in such hyperoxia-induced HVR potentiation, 17 male Sprague-Dawley adult ratsunderwent hypoxic challenges (10%O₂-5%CO₂-balanceN₂) preceded either by 10 min ofroom air (O₂) or of 100%O₂(+O₂). At least 48 h later,similar challenges were performed after the animals received theselective nNOS inhibitor 7-nitroindazole (25 mg/kg ip). InO₂ runs, minute ventilation(E)increased from 121.3 ± 20.5 (SD) ml/min in room air to 191.7 ± 23.8 ml/min in hypoxia (P < 0.01). After +O₂,E increasedfrom 114.1 ± 19.8 ml/min in room air to 218.4 ± 47.0 ml/min inhypoxia (+O₂ vs.O₂:P < 0.005, ANOVA). After7-nitroindazole administration, HVR was not affected in theO₂ treatment group withE increasingfrom 113.7 ± 17.8 ml/min in room air to 185.8 ± 35.0 ml/min inhypoxia (P < 0.01).However, HVR potentiation in+O₂-exposed animals was abolished(111.8 ± 18.0 ml/min in room air to 184.1 ± 35.6 ml/min inhypoxia; +O₂ vs.O₂:P not significant). We conclude that in the conscious rat nNOS activation mediates essential components ofthe HVR potentiation elicited by a previous short hyperoxic exposure.