The HVR had a classical biphasic stimulatory/inhibitory character in both healthy untreated and parkinsonic reserpine-treated rats. The peak V_E response developed promptly within 30 s from hypoxia commencement followed by a gradual fall-off; with ventilation remaining above the resting baseline level within the test time. Peak ventilatory augmentation at both hypoxic levels employed, as shown in all relevant figures below, was invariably significant (0.05 > p > 0.0001). Parkinsonic V_E was significantly dampened across the course of the hypoxic course compared with that in the healthy group (Fig. 2a, b). The dampening was present in response to both 12 % and 8 % hypoxia and was notably expressed in relation to the peak response at 30 s. The ventilatory response to the stronger 8 % hypoxic stimulus expectedly demonstrated a more conspicuous hyperpneic stimulation as well as reserpine-induced inhibition; where the mean peak V_E decreased from 1644 ± 82 ml∙min⁻¹∙kg⁻¹ in the healthy to 1264 ± 73 ml∙min⁻¹∙kg⁻¹ in the parkinsonic rats (p < 0.0001) (Fig. 2b). The parkinsonic condition also decreased the baseline resting V_E before the initiation of hypoxia. This decrease, albeit significant, was disproportionally smaller than that of peak V_E. Therefore, the dampening ventilatory effect of the parkinsonic condition was even more noticeable in the augmentation of V_E from baseline to peak amounting to 771 ± 52 and 532 ± 47 ml∙min⁻¹∙kg⁻¹ (p < 0.01) in the healthy and parkinsonic rats, respectively, in response to 8 % hypoxia. The three null hypotheses tested by two-way ANOVA that time has no effect on the ventilatory outcome, reserpine treatment makes no ventilatory difference, and there is no interaction between time and treatment regarding the ventilatory outcome were disproved (p < 0.001) (Fig. 2b). No differences between the effects of reserpine and reserpine + DOM were detected in the V_E responses to either 12 % or 8 % hypoxia.

Domperidone, a peripheral antagonist of DA D2 receptors which does not cross the blood-brain barrier, given on top of reserpine failed to appreciably influence baseline ventilation and its responses to hypoxia (Fig. 2a, b). That was in contrast to a waxing effect of domperidone on the HVR in the untreated healthy rats, which was particularly expressed during the stronger 8 % hypoxic stimulation (Fig. 3b).

Conversely, L-DOPA with benserazide, the latter inhibits peripheral L-DOPA metabolism which enables it to cross the blood-brain barrier in full, a central DA D2 receptor agonist, given on top of reserpine significantly enhanced reserpine-dampened resting ventilation and its responses in both mild and strong hypoxia (Fig. 4a, b). The enhancement exceeded, although insignificantly, the baseline ventilatory level over the course of the hypoxic responses, yielding a stimulatory response overshoot. The peak ventilatory responses to the stronger 8 % hypoxic stimulus at 30 s were as follows: baseline in the untreated rats of 1409 ± 62 ml∙min⁻¹∙kg⁻¹ decreased to 1017 ± 117 ml∙min⁻¹∙kg⁻¹ in reserpine-induced parkinsonism, and rebounded to 1661 ± 168 ml∙min⁻¹∙kg⁻¹ after giving L-DOPA with benserazide on top of reserpine; differences in V_E between reserpine-treated vs. untreated and reserpine + L-DOPA-treated rats were significant (p < 0.01) (Fig. 4b). There were significant treatment (p < 0.04) and time (p < 0.001) effects on the ventilatory outcome, and an interaction between the two (p < 0.001) regarding the HVR after reserpine vs. reserpine + L-DOPA for 12 % and 8 % hypoxia and the HVR in untreated vs. reserpine-treated rats for 8 % hypoxia (two-way ANOVA).

L-DOPA with benserazide given to otherwise untreated rats, showed just a tendency to enhance ventilation and its responses to both 12 % and 8 % hypoxia, which failed to reach significance across the response course (Fig. 5).

The inspection of the breathing pattern shows that the frequency component contributed more to shaping the ventilatory changes. Breathing rate decreased by about 30–40 % in reserpinized rats along the HVR. This decrease tended to be compensated by increases in tidal component, which were disproportionately smaller and thus fell short of offsetting the overall decrease in V_E (Table 1). Domperidone failed to affect the breathing patter. L-DOPA, on the other hand, increased both components, in particular breathing rate reverted, on average, about halfway toward the baseline level present in the healthy untreated condition.