Tsoukaris-Kupfer D, Girerd X, Laurent S, Legrand M, Huchet-Brisac A M, Schmitt H
Département de Pharmacologie Cardiovasculaire, Unité INSERM 228, Broussais-Hôtel Dieu, Paris, France.
J Cardiovasc Pharmacol. 1987;10 Suppl 10:S40-3.
The central cardiovascular effects of the calcium channel inhibitor (CCI) nifedipine and the calcium channel activator BAY k 8644 (BAY) were studied in pentobarbital-anesthetized and ventilated normotensive Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). Both drugs were administered under a 1.5 microliter volume into the lateral ventricle of the brain (intracerebroventricular, i.c.v.). The injection of vehicle (ethanol) alone did not significantly change mean arterial pressure (MAP) or heart rate (HR). Nifedipine (5 and 50 micrograms/kg) and BAY (5 and 50 micrograms/kg) induced opposite effects on MAP when centrally injected. Nifedipine decreased MAP and HR while BAY increased MAP without significant change in HR. These effects are likely to be of central origin, because they were suppressed by ganglionic blockade with hexamethonium and by reserpine. Previously i.c.v. administered nifedipine (5 micrograms/kg) antagonized pressor response to BAY (5 micrograms/kg i.c.v.). Changes in MAP and HR 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.
在戊巴比妥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，研究了钙通道抑制剂（CCI）硝苯地平和钙通道激活剂BAY k 8644（BAY）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，i.c.v.）。单独注射溶媒（乙醇）不会显著改变平均动脉压（MAP）或心率（HR）。当进行中枢注射时，硝苯地平（5和50微克/千克）和BAY（5和50微克/千克）对MAP产生相反的作用。硝苯地平降低MAP和HR，而BAY升高MAP，HR无显著变化。这些作用可能源于中枢，因为它们被六甲铵的神经节阻断和利血平抑制。先前脑室内注射的硝苯地平（5微克/千克）可拮抗对BAY（脑室内注射5微克/千克）的升压反应。SHR中MAP和HR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以以相反的方式调节参与血压控制的中枢机制。
