Role of nitric oxide in chronic intermittent hypoxia-induced changes in arterial chemoreflex and cardiovascular responses in spontaneously hypertensive rats

• Main Authors: Chung-Huan Yang, 楊昌寰
• Other Authors: Ching-Jung Lai
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/59367307917232825856

碩士 === 慈濟大學 === 生理暨解剖醫學研究所 === 97 === Obstructive sleep apnea (OSA) is associated with airway inflammation; an important role in this regard seems to be played by nitric oxide (NO) and peroxynrite, which is respectively induced by inducible NO synthase (iNOS) and interworked by NO and superoxide anion. Additionally, OSA occurs frequently in the hypertensive patients. In this study, we examined whether chronic intermittent hypoxia (CIH) (6 h/day, for 30 days) affects in arterial chemoreflex and cardiovascular responses in age-matched (8-9-wk-old) adult male spontaneously hypertensive rats (SHRs), and if so, determined whether activation of inducible NO synthase or peroxynitrite plays a critical role in mediating these cardiorespiratory responses. Blood pressure signals were measured daily by the telemetry system, which were used to assess the autonomic functions by heart rate variability analysis. Ventilatory responses during room air (RA) breathing and during acute hypoxic exposure (12% O2 for 5 min), indices for arterial chemoreflex sensitivities, were monitored daily by whole body plethysmograph. We found that intermittent hypoxia (IH) markedly increased the normalized low-frequency power of pulses interval spectrogram (LF%) (an index for cardiac sympathetic outflow) and mean arterial pressure in SHRs, whereas RA evoked only a mild elevation of these responses. Similarly, IH challenge exhibited significant increases in minute ventilation by breathing RA or acute hypoxia. However, no significant differences in high-frequency power of pulses interval spectrogram (HF) (an index for cardiac vagal activity) and heart rate were observed between these groups. These cardiorespiratory responses to IH were completely prevented by pretreatment with aminoguanidine, a selective inhibitor of iNOS or L-cysteine, a peroxynitrite scavenger, but was not affected by vehicle. These results suggest that exaggerated blood pressure response to IH may be associated with arterial chemoreflex activation and facilitation of sympathetic outflow, and activation of iNOS and peroxynitrite play an important role in CIH-induced these responses in conscious SHRs.