engleski

WAY-100635 attenuates phrenic long term facilitation in rats

Objectives: To investigate the effect of 5-HT1A receptor antagonist WAY-100635 on the phrenic long-term facilitation (pLTF) in rats. We hypothesized there would be a significant attenuation of pLTF in animals treated with WAY-100635 in comparison with control group of animals. Methods: Twenty one adult, male, urethane anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats (7 per group), were exposed to the acute intermittent hypoxia (AIH) protocol. Protocol consisted of 5 hypoxic episodes (9%O2), each lasting for 3 minutes. Experimental groups of animals WAY0 and WAY60 received an intravenous injection of WAY-100635, before the onset of the first hypoxic stimulus, and 60 minutes after the end of last hypoxia, respectively. Peak phrenic nerve amplitude (PNA), burst frequency (f), and breathing rhythm parameters (Ti, Te, Ttot) were analyzed during the first hypoxia, as well as at 15 (T15), 30 (T30), and 60 minutes (T60) after the end of the last hypoxic episode, and compared to the baseline values. Results: In control and WAY60 group, significant increases of PNA (58.7 ± 3.3%, p<0.001 and 45.6 ± 3.3%, p<0.001, respectively) at T60 were observed. After administration of WAY-100635 in group WAY60, PNA decreased to the baseline values. PNA of animals treated with WAY-100635 before the onset of the first hypoxia, showed a slight decrease at T60 by 15.1 ± 1.7%. Conclusion: The pLTF, elicited by AIH, was induced in control and in group WAY60. On the contrary, administration of WAY-100635 inhibited development and maintenance of pLTF in rats.

respiration; phrenic nerve; intermittent hypoxia; rats; neuronal plasticity; serotonin

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