N-acetylcysteine treatment prevents the enhanced cardiorespiratory response induced by intermittent hypoxia in normotensive and spontaneously hypertensive rats

Autor: Wen-hsuan Li, 李汶軒
Rok vydání: 2011
Druh dokumentu: 學位論文 ; thesis
Popis: 99
Long-term exposure to intermittent hypoxia (IH), such as that which occurs with obstructive sleep apnea (OSA), may be one factor contributing to systemic hypertension seen in OSA patients. Importantly, OSA occurs frequently in the hypertensive patients. IH seems to resemble hypoxia-reoxygenation, wherein cellular generation of reactive oxygen species (ROS). The present study attempted to evaluate the differences in arterial chemoreflex, cardiac autonomic modulations, and mean arterial pressure (MAP) among spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD) following IH exposure, and to determine the role of ROS involves in eliciting these cardiopulmonary alternations in these conscious unrestrained rats. We used age-matched (8-9-wk-old) adult male rats exposed to repetitive 1.25-min cycles (30 s of N2 + 45 s of 21% O2) of IH or room air (RA) for 6 h/day during light phase (10 AM-4 PM) for 30 days. Blood pressure signals were measured daily by the telemetry system, which were used to assess the autonomic function by MAP and heart rate variability analysis. Respiratory responses during RA breathing and acute hypoxia (12% O2), the indices for tonic and phasic chemoreflex activation, respectively, were measured daily using the barometric technique of plethysmography. WKY and SD had similar MAP, which is significantly lower than that of SHR after RA or IH exposure. Furthermore, SHR developed higher low-frequency power of the MAP spectrogram (BLF) (an index for sympathetic vasomotor activity) after RA or IH exposure. Among three strains of rats, IH did not induce changes in high-frequency power of pulses interval spectrogram (HF) (an index for cardiac vagal activity) and heart rate, but a similar increase in normalized low-frequency power of pulses interval spectrogram (LF%) (an index for cardiac sympathetic outflow). Additionally, IH challenge exhibited a similar and significant increase in minute ventilation (an index for arterial chemoreflex activation) and FosB expression in caudal nucleus tractus solitarius (cNTS) in three strains of rats. Intraperitoneal injection of N-acetylcysteine (an antioxidant, 250 mg/kg, i.p.) totally prevented IH-induced the elevations of the cardiorespiratory responses and FosB expression in cNTS. These results suggest that 1) IH-induced hypertension may be associated with arterial chemoreflex activation and facilitation of sympathetic outflow in three different strains of rats; and 2) ROS may involve in IH-induced these cardiorespiratory responses.
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