Effects of hydralazine and adenosine receptor agonists on the sleep apnea in spontaneously hypertensive rats

• Main Author: 游欣儀
• Other Authors: 賴靜蓉
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/52084961794625626724

碩士 === 慈濟大學 === 神經科學研究所 === 91 === Increased prevalence of sleep-disordered respiration has been reported in patients with essential hypertension and in animal model of genetically hypertensive rats. Additionally, previous studies reported that acute pharmacological normalization of blood pressure could improve sleep apneas; further adenosine receptor agonist could treatment of sleep apnea indirectly by causing hypotension and stimulates peripheral chemoreceptors. However, the relationship between sleep-disordered respiration and hypertension is still largely unclear. The objectives of the study were (1) to test the hypothesis that acute pharmacological normalization of blood pressure would decrease the expression of sleep apneas, (2) to investigate whether the combination effect on the inhibition of sleep apneas by adenosine receptor agonists, causing both reduce blood pressure and stimulate peripheral chemoreceptors in spontaneously hypertensive rats (SHR). Adult male SHR were surgically prepared with cortical electroencephalogram, nuchal electromyogram and diaphragm electromyogram to monitor sleep stages and respiration. Each rat was recorded from 1000 until 1600 on different days by intraperitoneal administration of hydralazine (a vasodilator), CPA (an A1 adenosine receptor agonist) and CGS21680 (an A2 adenosine receptor agonist). We found that sleep architecture was not affected by pretreatment with vehicle or drugs administration. The effects of lowering blood pressure by hydralazine and adenosine agonists lasted for 3 hr and 50 min, respectively. Postsigh apnea occurred more frequently than did spontaneous apnea in all sleep stages following vehicle or drugs administration. The sleep-related apnea index was decreased by pretreatment with hydralazine, CGS21680 or CPA. In addition, a prior administration of hydralazine, CGS21680 or CPA had a more pronounced effect on the spontaneous apneas than on the postsigh apneas. Furthermore, either spontaneous apnea or postsigh apnea had a more enhanced effect after denervation of bilateral carotid sinus nerves. In addition, inhibition of spontaneous sleep apnea by CGS21680 and CPA was significantly attenuated by denervation of bilateral carotid sinus nerves. Taken together, these results suggest that (1) pharmacological normalization of blood pressure might reduce sleep apneas in SHR, and that (2) adenosine plays a significant role in modulation of sleep apnea expression which, in part, involves a stimulation of peripheral chemoreceptors.