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

S Laurent, X Girerd, D Tsoukaris-Kupfer, M Legrand, A M Huchet-Brisac, H Schmitt
1987 Hypertension  
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.
more » ... 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
doi:10.1161/01.hyp.9.2.132 pmid:2434422 fatcat:32rv6gnmhbctze2babwwq7frvi