Glatt C E, Kenner J R, Long J B, Holaday J W
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Peptides. 1987 Nov-Dec;8(6):1089-92. doi: 10.1016/0196-9781(87)90141-0.
The short-term cardiovascular effects of dynorphin A (1-13), as well as its effects upon morphine bradycardia were investigated. In unanesthetized, unrestrained rats, intracerebroventricular (ICV) dynorphin A (1-13) injections (10-20 micrograms) produced a dose-related pressor effect, whereas intravenous (IV) dynorphin A (1-13) (1.0 mg/kg) produced a depressor effect; these responses persisted less than five min. Heart rate was not significantly altered by these doses or routes of administration. Dynorphin A (1-13) also produced behavioral effects in the unanesthetized animals, such as wet dog shakes in response to IV administration and wet dog shakes accompanied by barrel rolling in response to ICV administration. To evaluate the effects of dynorphin A (1-13) pretreatment on the bradycardic response to IV morphine, rats were pretreated with 10 micrograms dynorphin A (1-13) ICV four, six or eight hours prior to challenge with morphine sulfate (0.1 mg/kg IV). Four hour pretreatment with dynorphin A (1-13) (tested at 14:00 hr) resulted in a potention of morphine bradycardia, with six hours pretreatment (tested at 16:00 hr) no effect was observed, and eight hours following dynorphin A (1-13) pretreatment (tested at 18:00 hr) morphine bradycardia was attenuated. Additionally, the bradycardic response to IV morphine alone became more exaggerated as rats approached their nocturnal activity cycle. These data further establish that dynorphin A (1-13) exerts a potent, long lasting modulatory effect on morphine bradycardia and emphasize the importance of circadian variables in altering the magnitude of cardiovascular responses to opioid agonists.
研究了强啡肽A（1 - 13）的短期心血管效应及其对吗啡所致心动过缓的影响。在未麻醉、未束缚的大鼠中，脑室内（ICV）注射强啡肽A（1 - 13）（10 - 20微克）产生剂量相关的升压效应，而静脉注射（IV）强啡肽A（1 - 13）（1.0毫克/千克）产生降压效应；这些反应持续时间不到五分钟。这些剂量或给药途径未显著改变心率。强啡肽A（1 - 13）在未麻醉动物中也产生行为效应，如静脉注射后出现湿狗样抖动，脑室内注射后出现伴有翻滚的湿狗样抖动。为了评估强啡肽A（1 - 13）预处理对静脉注射吗啡所致心动过缓反应的影响，在给予硫酸吗啡（0.1毫克/千克静脉注射）激发前四、六或八小时，给大鼠脑室内注射10微克强啡肽A（1 - 13）进行预处理。强啡肽A（1 - 13）预处理四小时（14:00测试）导致吗啡所致心动过缓增强，预处理六小时（16:00测试）未观察到影响，强啡肽A（1 - 13）预处理八小时后（18:00测试）吗啡所致心动过缓减弱。此外，随着大鼠接近夜间活动周期，单独静脉注射吗啡所致的心动过缓反应变得更加明显。这些数据进一步证实强啡肽A（1 - 13）对吗啡所致心动过缓具有强大、持久的调节作用，并强调了昼夜节律变量在改变对阿片类激动剂心血管反应强度方面的重要性。
