Effects of progesterone on apneic events during behaviorally defined sleep in male rats.
Drug therapy with progesterone has been applied to the patients with sleep apnea syndrome, but its clinical efficacy is equivocal. In the present study, we examined the effects of progesterone (1 and 30 mg/kg, i.p.) on the apneic events during behaviorally defined sleep in male rats at 4, 14 and 26 weeks of age by using a whole body plethysmographic measurement. The number of events of spontaneous apnea (SA) and post-sigh apnea (PSA) increased with aging. The duration of SA or PSA was also prolonged in old rats. A low dose (1 mg/kg) of progesterone significantly decreased the number of both SA and PSA, and this effect increased in an age-dependent manner. However, progesterone had no effect on the duration of SA and PSA. Neither the basal respiratory rate nor the total sleep time was changed. On the other hand, a higher dose (30 mg/kg) of progesterone had no effect on the number of SA and PSA, while it prolonged the duration of PSA. It also prolonged the total sleep time without affecting the basal respiratory rate. Pretreatment with mifepristone (5 mg /kg, i.p.), an antagonist of progesterone receptors, inhibited the effects of the low dose of progesterone, but did not show any antagonistic effect on the high dose-induced changes. These results suggest that the progesterone-mediated mechanisms are involved, at least partly, in respiratory function during sleep and the progesterone therapy is possibly effective within an appropriate dose range for the sleep apnea syndrome.
Yamazaki
Hiromi
H
Department of Pharmacology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. mp03hy@ms.toyama-mpu.ac.jp
Haji
Akira
A
Ohi
Yoshiaki
Y
Takeda
Ryuji
R
D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D006727:Hormone Antagonists / Q000494:pharmacology; D006985:Hyperventilation / Q000188:drug therapy / Q000209:etiology; D007274:Injections, Intraperitoneal; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D010993:Plethysmography, Whole Body; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012891:Sleep Apnea Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
D006727:Hormone Antagonists; D015735:Mifepristone; D011374:Progesterone