SUMMARY 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-/U.1 volume into the lateral ventricle of the brain (i.c.v.) or into the cisterna magna (i.e.). The injection of vehicle alone (i.e. or i.c.v.) did not significantly change mean arterial pressure (MAP) or heart rate. Nifedipine (5 and 50 /ug/kg) and BAY k 8644 (5 and SO fig/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.e.), and BAY k 8644 increased MAP without any significant change in heart rate (i.e. 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 gang!ionic 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 /u.g/kg) antagonized the pressor response to BAY k 8644 (5 jug/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. (Hypertension 9: 132-138. 1987) KEY WORDS • 1,4-dihydropyridine • calcium channel blocker • spontaneously hypertensive rats • central nervous system • BAY k 8644 C ALCIUM channel blockers produce an in vitro direct depression of myocardial contractility and sinus node automaticity as well as relaxation of isolated coronary and peripheral blood vessels 1 ' 2 by inhibiting calcium influx into the cells. 3 The direct effects of calcium channel blockers on cardiovascular function can be modifed by their effects on the autonomic nervous system. 4 Calcium channel blockers have been reported to act peripherally to decrease neurotransmitter release at the neuromuscular junction 5 -6 and to modulate carotid baroreceptor function.7 Some evidence suggests that calcium channel blockers influence the autonomic nervous system at the central level, thus altering cardiovascular function.

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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-/U.1 volume into the lateral ventricle of the brain (i.c.v.) or into the cisterna magna (i.e.). The injection of vehicle alone (i.e. or i.c.v.) did not significantly change mean arterial pressure (MAP) or heart rate. Nifedipine (5 and 50 /ug/kg) and BAY k 8644 (5 and SO fig/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.e.), and BAY k 8644 increased MAP without any significant change in heart rate (i.e. 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 gang!ionic 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 /u.g/kg) antagonized the pressor response to BAY k 8644 (5 jug/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. (Hypertension 9: 132-138. 1987) KEY WORDS • 1,4-dihydropyridine • calcium channel blocker • spontaneously hypertensive rats • central nervous system • BAY k 8644 C ALCIUM channel blockers produce an in vitro direct depression of myocardial contractility and sinus node automaticity as well as relaxation of isolated coronary and peripheral blood vessels 1 ' 2 by inhibiting calcium influx into the cells. 3 The direct effects of calcium channel blockers on cardio-vascular function can be modifed by their effects on the autonomic nervous system. 4 Calcium channel blockers have been reported to act peripherally to decrease neurotransmitter release at the neuromuscular junction 5-6 and to modulate carotid baroreceptor function. 7 Some evidence suggests that calcium channel blockers influence the autonomic nervous system at the central level, thus altering cardiovascular function.