Enhanced carotid hypoxic chemosensitivity in chronic intermittent hypoxic rats: a potential role of nitric oxide

Abstract

Increased carotid chemosensitivity has been documented in rats subjected to chronic intermittent hypoxia (CIH). The mechanisms underlying are unclear. Nitric oxide (NO) is an inhibitory neurotransmitter of carotid chemoreceptor activity (CCA). Our previous studies demonstrated that CIH decreased the expression of neuronal nitric oxide synthase (nNOS), an enzyme of NO biosynthesis in rat carotid bodies. The present study aimed to determine whether the increased chemoreceptor gain might be related to the changes in NO production. Sprague-Dawley rats were exposed to either normoxia (21% O2) or CIH (7.5–10% O2 for 1 min of every 4 min) for 8 hours/day for 5 weeks. Chemoreceptor discharges were recorded from the carotid sinus nerve in anesthetized and mechanically ventilated rats. The discharge frequency in hyperoxic state (400–450 Torr) was reduced more in CIH rats than in sham rats. Consistent with previous studies, the CCA responses to two levels of hypoxia (30–60 Torr) were greater in the exposed rats relative to sham animals. Intracarotid administration of 0.3 mg/kg of NG-nitrio-L-arginine (L-NNA), a nonspecific nitric oxide synthase (NOS) inhibitor markedly increased the CCA response to hypoxia in both groups but L-NNA had a less effect on the animals exposed to CIH. A large dose (100mg/kg) of L-arginine, the endogenous substrate for NOS significantly attenuated the chemoreceptor response to hypoxia and reversed the effect of L-NNA by intracarotid injection. These data suggest that an impairment of NO production by decreased nNOS expression likely contributes to enhanced carotid chemoreceptor activity in this model. Supported by NIH-R01 HL75184-01.