Debrisoquine is a peripherally acting monoaminooxidase A (MAO-A) inhibitor. MAO is, in cooperation with the catecholO-methyltransferase (COMT), the main enzyme degradating dopamine in vivo. Dopamine itself is one of the most important neurotransmitters involved in the generation of the respiratory response to hypoxia. Our study seeks to determine whether blockade of the MAO-pathway, resulting in an augmentation of the endogenous dopamine content, could influence the respiratory response to hypoxia in conscious rats. We performed the experiments in 8 male adult Wistar rats (10-11 weeks old, 290-310 g). Minute lung ventilation and its responses to 8 and 12% hypoxic stimuli were measured in a BUXCO whole body plethysmographic chamber. After the control recordings had been taken, debrisoquine (40 mg/kg, i.p.) was injected and the responses to both stimuli were reevaluated after 30 and 60 min. We found that debrisoquine, after 30 min, significantly increased the peak hypoxic ventilatory response (HVR) from 1109 ±161 and 1320±194 to 1744±265 and 2307±259 ml/min/kg for 8% and 12% hypoxia, respectively. However, this effect failed to be long-lasting: 60 min post-injection the peak respiratory response regressed to 1312±135 and 1681 ±105 ml/min/kg, for 8 and 12% hypoxia, respectively. These results indicate that a peripheral blockade of MAO-A increases the HVR. A possible explanation of this phenomenon is the putative stimulatory action of endogenous dopamine (at higher concentrations) or activation by debrisoquine some other stimulatory, non-amine neurotransmitters which do not undergo a MAO-linked oxidation, in the generation of the hypoxic response peripherally at the level of the carotid body. Yet another explanation could be by far unknown, stimulatory influence of debrisoquine on respiration.
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