[Central cardiovascular effects of a calcium inhibitor, nifedipine, and a calcium channel activator, Bay k 8644, in the anesthetized rat].
The antihypertensive effect of calcium channel inhibitors (CCI) results mainly from their direct action on the vascular smooth muscle. However CCI may pass through the blood-brain barrier and may modulate central mechanisms involving calcium channels. Normotensive (WKY) and spontaneously hypertensive (SHR) (Okamoto) rats weighing 300 g were anaesthetized with pentobarbital (50 mg/kg i.p.) and ventilated. Mean arterial pressure (MAP) was measured from a catheter inserted into the femoral artery. Heart rate (HR) was electronically integrated. Vehicle (ethanol 95%), nifedipine and Bay k 8644 (Bay) were injected under a 1.5 microliter volume into the lateral ventricle of the brain (i.c.v.). Vehicle alone did not change significantly MAP or HR. The calcium-channel inhibitor nifedipine and the calcium-channel activator Bay had opposite effects, when i.c.v. injected: hypotension with bradycardia and hypertension without tachycardia, respectively. These effects are dose-dependent (5-50 micrograms/kg). They are of central origin since they are suppressed by ganglionic blockade by hexamethonium(100 mg/kg i.c.). Bilateral vagotomy suppressed the i.c.v.-nifedipine induced bradycardia. Previously i.c.v. administered nifedipine (5 micrograms/kg) suppressed the pressor response to Bay (5 micrograms/kg i.c.v.). Changes in MAP and HR are 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 calcium-dependent mechanisms involved in blood pressure control.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000008:administration & dosage; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains
D006584:Hexamethonium Compounds; D018738:Hexamethonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine
Effets cardiovasculaires centraux d'un inhibiteur calcique, la nifédipine, et d'un activateur des canaux calciques, le BAY k 8644, chez le rat anesthésié.