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 whether neuronal nitric oxide synthase (nNOS) is involved in such hyperoxia-induced HVR potentiation, 17 male Sprague-Dawley adult rats underwent hypoxic challenges (10% O2-5% CO2-balance N2) preceded either by 10 min of room air (-O2) or of 100% O2 (+O2). At least 48 h later, similar challenges were performed after the animals received the selective nNOS inhibitor 7-nitroindazole (25 mg/kg ip). In -O2 runs, minute ventilation (VE) 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, VE increased from 114.1 +/- 19.8 ml/min in room air to 218.4 +/- 47. 0 ml/min in hypoxia (+O2 vs. -O2: P < 0.005, ANOVA). After 7-nitroindazole administration, HVR was not affected in the -O2 treatment group with VE increasing from 113.7 +/- 17.8 ml/min in room air to 185.8 +/- 35.0 ml/min in hypoxia (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 in hypoxia; +O2 vs. -O2: P not significant). We conclude that in the conscious rat nNOS activation mediates essential components of the HVR potentiation elicited by a previous short hyperoxic exposure.