Effect Of Tetramethylpyrazine On The Responses Of Respiration And Expression Of NNOS In The Brainstem To Hypoxia In Rats

In the present study, the experiments were performed on adult Sprague-Dawley rats (250-300g). The hypoxia of the rats was induced by inhalation of 8%02-balanced N2. The electromyogram (EMG) of the diaphragm and the blood pressure of the femoral artery were monitored to evaluate the responses of respiration and the blood pressure of the rats to hypoxia and the role of tetramethylpyrazine (TMP) in the changes in the respiration and blood pressure. The immunohistochemical staining technique was used to study the change in the expression of neuronal nitric oxide synthase (nNOS) in the brainstem induced by hypoxia. The aims of this study were to investigate (1) whether TMP plays a protective effect on the hypoxic respiratory depression and (2) whether nNOS in the brainstem is involved in the protective mechanism. The main results were as follows.1. Effect of Hypoxia on Respiratory Activity of Rats and Influence of TMP on the Effect.In the rats with purely hypoxia, a successive process of respiratory responses, excitation followed by inhibition, was induced. After 20 min of hypoxia, a significant inhibition of respiration occurred, which was characterized with marked decreases in the inspiratory duration (TI), the respiratory frequency (RF) and the amplitude of inspiration (Amp) and a prolongation of the expiratory duration (TE) (P<0.05). Compared with the rats with purely hypoxia, in the rats pretreated with TMP, the degrees of the changes in the respiratory indices induced by hypoxia mentioned above were notably reduced (P<0.05). The changes in the partial pressure and saturation of oxygen (PO2 and C^Saf) and partial pressure of carbon dioxide in the arterial blood were induced in a corresponding manner.2. Effect of Hypoxia on Femoral Arterial Blood Pressure of Rats and Influence of TMP on the Effect.In either the rats with hypoxia or the rats pretreated with TMP, a decrease in the femoral arterial blood pressure was induced by hypoxia (P<0.05). Compared with the rats with purely hypoxia, the degree of the decrease in the blood pressure was lowered in the rats pretreated with TMP (PO.05) at 1 min during hypoxia.3. Effect of Hypoxia on Expression of nNOS in Brainstem of Rats and Influence of TMP on the Effect.The nNOS-positive immunoreactive neurons could be observed in the lateral reticular nucleus, nucleus of trapezoid, nucleus of solitary tract and nucleus of ambiguous in any group of the rats, the air controlgroup, the purely TMP group, the purely hypoxia group or the hypoxia group pretreated with TMP. The level of nNOS immunoreactivity was remarkably enhanced by hypoxia (PO.05) and enhanced further more by TMP (PO.05).It c an b e c oncluded t hat T MP c ould d elay t he o ccurrence o f t he inhibitory effect of hypoxia on respiration in the rats and decrease the degree of hypoxic respiratory depression, indicating a protective role of TMP in the hypoxic respiratory inhibition, and that the nitric oxide (NO) derived from nNOS in the nuclei of the brainstem may be involved in the respiratory protective mechanism of TMP.