Central and peripheral cardiovascular effects of the enantiomers of the calcium antagonist PN 200-110.
The negative inotropic effects and the central and peripheral hypotensive effects of (+) and (-) PN 200-110 were investigated in cultured chick heart cells and in spontaneously hypertensive rats, respectively. There was a large difference in negative inotropic potency between the two enantiomers in cultured chick embryo ventricular cells: the (+) enantiomer was 140 fold more potent (IC50 = 1.1 +/- 0.2 nM) than the (-) enantiomer (IC50 = 160 +/- 20 nM). (+) PN 200-110 was 10 fold more potent than (-) PN 200-110 in lowering blood pressure after intravenous injection and only three fold more potent after intra-cerebroventricular injection (i.c.v.) into pentobarbital-anaesthetized spontaneously hypertensive rats. I.c.v. administered (+) PN 200-110 (1 microgram/kg) partially antagonized the hypertensive response to i.c.v. administered BAY K 8644 (30 micrograms/kg), a calcium channel agonist, while the same dose of the (-) enantiomer did not change the i.c.v. BAY-induced increase in blood pressure. These results suggest that the dihydropyridine calcium channel antagonist, PN 200-110, may act centrally and stereoselectively at the level of the dihydropyridine receptor sites involved in the control of blood pressure in spontaneously hypertensive rats.
Briand
V
V
Laboratoire de Pharmacologie Cardiovasculaire, INSERM U 228, Paris, France.
Laurent
S
S
Tsoucaris-Kupfer
D
D
Legrand
M
M
Brisac
A M
AM
Schmitt
H
H
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D017275:Isradipine; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D010069:Oxadiazoles; D017275:Isradipine