Opposite central cardiovascular effects of nifedipine and BAY k 8644 in anesthetized rats

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.