Laurent S, Girerd X, Tsoukaris-Kupfer D, Legrand M, Huchet-Brisac A M, Schmitt H
Hypertension. 1987 Feb;9(2):132-8. doi: 10.1161/01.hyp.9.2.132.
The central cardiovascular effects of the calcium channel blocker nifedipine and the calcium channel activator BAY k 8644 were studied in anesthetized and ventilated normotensive Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). Both drugs were administered in a 1.5-microliter volume into the lateral ventricle of the brain (i.c.v.) or into the cisterna magna (i.c.). The injection of vehicle alone (i.c. or i.c.v.) did not significantly change mean arterial pressure (MAP) or heart rate. Nifedipine (5 and 50 micrograms/kg) and BAY k 8644 (5 and 50 micrograms/kg) induced opposite effects on MAP when centrally injected. Nifedipine decreased MAP and induced a bradycardia (i.c.v.) or no change in heart rate (i.c.), and BAY k 8644 increased MAP without any significant change in heart rate (i.c. or i.c.v.). These effects were more marked with the highest dose of either drug. These effects seemed to be of central origin, since they were suppressed by ganglionic blockade by hexamethonium (100 mg/kg i.v.), whereas after hexamethonium the hypotensive and the hypertensive responses to intravenously injected nifedipine and BAY k 8644, respectively, were preserved. Bilateral vagotomy suppressed the bradycardia induced by i.c.v. administered nifedipine. Previously i.c.v. administered nifedipine (5 micrograms/kg) antagonized the pressor response to BAY k 8644 (5 micrograms/kg i.c.v.). Changes in MAP and heart rate were significantly more marked in SHR than in WKY. These results indicate that a calcium channel inhibitor and a calcium channel activator can modulate in opposite fashion central mechanisms involved in blood pressure control.
在麻醉并通气的正常血压Wistar-Kyoto（WKY）大鼠或自发性高血压大鼠（SHR）中，研究了钙通道阻滞剂硝苯地平和钙通道激活剂BAY k 8644对心血管系统的中枢作用。两种药物均以1.5微升的体积注入脑侧脑室（脑室内）或小脑延髓池（脑池内）。单独注射赋形剂（脑池内或脑室内）不会显著改变平均动脉压（MAP）或心率。脑室内注射时，硝苯地平（5和50微克/千克）和BAY k 8644（5和50微克/千克）对MAP产生相反的作用。硝苯地平降低MAP并引起心动过缓（脑室内）或心率无变化（脑池内），而BAY k 8644升高MAP且心率无显著变化（脑池内或脑室内）。两种药物的最高剂量时这些作用更明显。这些作用似乎起源于中枢，因为六甲铵（100毫克/千克静脉注射）的神经节阻断可抑制它们，而六甲铵给药后，静脉注射硝苯地平和BAY k 8644分别引起的降压和升压反应得以保留。双侧迷走神经切断术可抑制脑室内注射硝苯地平引起的心动过缓。预先脑室内注射硝苯地平（5微克/千克）可拮抗对BAY k 8644（5微克/千克脑室内注射）的升压反应。SHR中MAP和心率的变化比WKY中明显更显著。这些结果表明，钙通道抑制剂和钙通道激活剂可通过相反的方式调节参与血压控制的中枢机制。
