Central modulation of baroreceptor reflex response to phenylephrine by dihydropyridines in rats.
The effects of two dihydropyridine derivatives, the calcium channel agonist BAY k 8644 or the antagonist PN 200-110, on the central nervous components of the baroreceptor reflex control of heart rate during activation of baroreceptors by phenylephrine (2 micrograms i.v.) were studied in pentobarbital-anesthetized normotensive (Wistar) rats and spontaneously hypertensive rats (SHR). To rule out an effect on peripheral vessels or on the sinoauricular node (or on both), BAY k 8644 and PN 200-110 were administered intracerebroventricularly (i.c.v.) at doses that did not change blood pressure. Baroreceptor reflex sensitivity was calculated as the slope of the relationship between systolic arterial pressure and heart period. Baroreceptor reflex sensitivity increased with time following the onset of anesthesia. In SHR, injection of BAY k 8644 (3 micrograms/kg i.c.v.) suppressed the time-dependent increase in baroreceptor reflex sensitivity. The inhibitory effect of BAY k 8644 (3 micrograms/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with PN 200-110 (0.6 microgram/kg i.c.v.) but not with the solvent, indicating that the central effect of BAY k 8644 occurred at the level of specific dihydropyridine binding sites. In addition, the inhibitory effect of BAY k 8644 (3 micrograms/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with the muscarinic antagonist atropine methylnitrate (80 micrograms/kg i.c.v.) but not with the solvent. In normotensive rats, the time-dependent increase in baroreceptor reflex sensitivity was not significantly altered by BAY k 8644 (3 micrograms/kg i.c.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
Lacolley
P
P
From the Laboratoire de Neuro Pharmacologie Cardiovasculaire, Institut National de la Santé et de la Recherche Médicale, 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 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D017275:Isradipine; D008297:Male; D009116:Muscarine / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012018:Reflex / Q000502:physiology*
D001286:Atropine Derivatives; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D010069:Oxadiazoles; D010656:Phenylephrine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009116:Muscarine; C006649:methylatropine; D017275:Isradipine