Breathing impairments, such as an alteration in breathing
pattern, dyspnoea, and sleep apnoea, are common health deficits
recognised in Parkinson’s disease (PD). The mechanism that
underlies these disturbances, however, remains unclear. We
investigated the effect of the unilateral damage to the rat
nigrostriatal pathway on the central ventilatory response to
hypercapnia, evoked by administering 6-hydroxydopamine
(6-OHDA) into the right medial forebrain bundle (MFB). The
respiratory experiments were carried out in conscious animals in
the plethysmography chamber. The ventilatory parameters were
studied in normocapnic and hyperoxic hypercapnia before and
14 days after the neurotoxin injection. Lesion with the 6-OHDA
produced an increased tidal volume during normoxia. The
magnified response of tidal volume and a decrease of breathing
frequency to hypercapnia were observed in comparison to the
pre-lesion and sham controls. Changes in both respiratory
parameters resulted in an increase of minute ventilation of the
response to CO2 by 28 % in comparison to the pre-lesion state
at 60 s. Our results demonstrate that rats with implemented
unilateral PD model presented an altered respiratory pattern
most often during a ventilatory response to hypercapnia.
Preserved noradrenaline and specific changes in dopamine and
serotonin characteristic for this model could be responsible for
the pattern of breathing observed during hypercapnia.
Carbon dioxide interacts both with reactive nitrogen species and reactive oxygen species. In the presence of superoxide, NO reacts to form peroxynitrite that reacts with CO2 to give nitrosoperoxycarbonate. This compound rearranges to nitrocarbonate which is prone to further reactions. In an aqueous environment, the most probable reaction is hydrolysis producing carbonate and nitrate. Thus the net effect of CO2 is scavenging of peroxynitrite and prevention of nitration and oxidative damage. However, in a nonpolar environment of membranes, nitrocarbonate undergoes other reactions leading to nitration of proteins and oxidative damage. When NO reacts with oxygen in the absence of superoxide, a nitrating species N2O3 is formed. CO2 interacts with N2O3 to produce a nitrosyl compound that, under physiological pH, is hydrolyzed to nitrous and carbonic acid. In this way, CO2 also prevents nitration reactions. CO2 protects superoxide dismutase against oxidative damage induced by hydrogen peroxide. However, in this reaction carbonate radicals are formed which can propagate the oxidative damage. It was found that hypercapnia in vivo protects against the damaging effects of ischemia or hypoxia. Several mechanisms have been suggested to explain the protective role of CO2 in vivo. The most significant appears to be stabilization of the iron-transferrin complex which prevents the involvement of iron ions in the initiation of free radical reactions., A. Veselá, J. Wilhelm., and Obsahuje bibliografii