Lacolley P, Laurent S, Tsoucaris-Kupfer D, Legrand M, Brisac A M, Schmitt H
From the Laboratoire de Neuro Pharmacologie Cardiovasculaire, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Hypertension. 1988 Sep;12(3):279-86. doi: 10.1161/01.hyp.12.3.279.
The effects of two dihydropyridine derivatives, the calcium channel agonist BAY k 8644 or the antagonist PN 200-110, on the central nervous components of the baroreceptor reflex control of heart rate during activation of baroreceptors by phenylephrine (2 micrograms i.v.) were studied in pentobarbital-anesthetized normotensive (Wistar) rats and spontaneously hypertensive rats (SHR). To rule out an effect on peripheral vessels or on the sinoauricular node (or on both), BAY k 8644 and PN 200-110 were administered intracerebroventricularly (i.c.v.) at doses that did not change blood pressure. Baroreceptor reflex sensitivity was calculated as the slope of the relationship between systolic arterial pressure and heart period. Baroreceptor reflex sensitivity increased with time following the onset of anesthesia. In SHR, injection of BAY k 8644 (3 micrograms/kg i.c.v.) suppressed the time-dependent increase in baroreceptor reflex sensitivity. The inhibitory effect of BAY k 8644 (3 micrograms/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with PN 200-110 (0.6 microgram/kg i.c.v.) but not with the solvent, indicating that the central effect of BAY k 8644 occurred at the level of specific dihydropyridine binding sites. In addition, the inhibitory effect of BAY k 8644 (3 micrograms/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with the muscarinic antagonist atropine methylnitrate (80 micrograms/kg i.c.v.) but not with the solvent. In normotensive rats, the time-dependent increase in baroreceptor reflex sensitivity was not significantly altered by BAY k 8644 (3 micrograms/kg i.c.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
在戊巴比妥麻醉的正常血压（Wistar）大鼠和自发性高血压大鼠（SHR）中，研究了两种二氢吡啶衍生物（钙通道激动剂BAY k 8644或拮抗剂PN 200 - 110）对去氧肾上腺素（静脉注射2微克）激活压力感受器期间心率压力感受器反射控制的中枢神经成分的影响。为排除对外周血管或窦房结（或两者）的影响，以不改变血压的剂量脑室内（i.c.v.）给予BAY k 8644和PN 200 - 110。压力感受器反射敏感性计算为收缩期动脉压与心动周期之间关系的斜率。麻醉开始后，压力感受器反射敏感性随时间增加。在SHR中，注射BAY k 8644（3微克/千克i.c.v.）抑制了压力感受器反射敏感性随时间的增加。PN 200 - 110（0.6微克/千克i.c.v.）预处理可抑制BAY k 8644（3微克/千克i.c.v.）对压力感受器反射敏感性随时间增加的抑制作用，但溶剂预处理则无此作用，表明BAY k 8644的中枢作用发生在特定二氢吡啶结合位点水平。此外，毒蕈碱拮抗剂硝酸甲基阿托品（80微克/千克i.c.v.）预处理可抑制BAY k 8644（3微克/千克i.c.v.）对压力感受器反射敏感性随时间增加的抑制作用，但溶剂预处理则无此作用。在正常血压大鼠中，BAY k 8644（3微克/千克i.c.v.）对压力感受器反射敏感性随时间的增加无显著影响。（摘要截短于250字）
