[Central control of the baroreflex response to phenylephrine by dihydropyridines in the anesthetized rat].
We have previously shown that a calcium channel activator (BAY K 8644) and a calcium channel inhibitor (CCI) (nifedipine), both dihydropyridine derivatives (DHP), can modulate in opposite fashion calcium dependent mechanisms involved in the central control of blood pressure and heart rate in SHR but not in Wistar rats. These results suggested that central DHP receptor sites might modulate baroreflex function. Therefore, we studied in pentobarbital anaesthetized SHR, the effects of BAY K 8644 and PN (200-110) (CCI) on central integration of baroreflex function (ramp method: phenylephrine 2 microgram i.v.). In order to rule out peripheral vascular effects, BAY and PN were administered intracerebroventricularly (i.c.v.) at doses which did not change BP. Baroreflex sensitivity (BRS) increased with time following the onset of anesthesia. In SHR, i.c.v. injection of BAY (3 microgram/kg) but not PN (0.6 micrograms/kg) suppressed the time dependent increase in BRS. The inhibitory effect of BAY on the time-dependent increase in BRS was suppressed by a pretreatment with PN (0.6 micrograms/kg i.c.v.) and by a pretreatment with the muscarinic antagonist atropine methylnitrate (80 micrograms/kg i.c.v.). BAY i.c.v. dit not change BRS in Wistar rats. These results indicate that DHP may centrally modulate BRS in SHR and suggest a central sympatho-excitatory effect for BAY mediated by an enhanced release of acetylcholine.
Lacolley
P
P
Laboratoire de pharmacologie et INSERM U 228, Paris, France.
Laurent
S
S
Tsoucaris-Kupfer
D
D
Legrand
M
M
Brisac
A M
AM
Schmitt
H
H
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; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels; D004095:Dihydropyridines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D015220:Calcium Channels; D004095:Dihydropyridines; D011978:Receptors, Nicotinic; D010656:Phenylephrine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium
Contrôle central de la réponse baroréflexe à la phényléphrine par les dihydropyridines chez le rat anesthésié.