Different effects of mibefradil and amlodipine on coronary vessels and during beta-adrenergic stimulation in conscious dogs.
Coronary effects of Ca -channel blockers mibefradil and amlodipine were compared in conscious dogs. Ten dogs were instrumented for measurement of aortic and left ventricular pressures, circumflex coronary blood flow velocity (CBFv), and coronary diameter (CD). A permanent catheter was implanted in the circumflex coronary artery. At doses having no systemic effects (7.5-150 micro g/kg), mibefradil and amlodipine increased CBFv and CD dose dependently. At the same dose, mibefradil increased less CBFv than amlodipine. However, for a similar increase in CBFv induced by amlodipine, mibefradil increased CD more. BAY K8644, an L-type Ca -channel agonist, prevented the CBFv and CD responses to amlodipine, but minimally affected the coronary responses to mibefradil. Intracoronary isoproterenol (6 ng/kg) increased LV dP/dt max, CBFv, and CD. Amlodipine markedly altered these responses, while mibefradil did not affect LV inotropic response and slightly altered CBFv response to isoproterenol. Thus, in conscious dogs, both mibefradil and amlodipine exert coronary vasodilation, with different patterns on coronary conductance and resistance vessels and during beta-adrenergic stimulation. These differences could be related to their actions on different Ca channels.
Heloire
François
F
INSERUM U400, Facultè de Mèdecine, 94010 Crèteil, France.
Hittinger
Luc
L
Champagne
Stéphane
S
Suto
Yukio
Y
Houel
Rémi
R
Ennezat
Pierre-Vladimir
PV
Sambin
Lucien
L
Crozatier
Bertrand
B
Su
Jin Bo
JB
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004347:Drug Interactions; D004558:Electric Stimulation; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D020748:Mibefradil / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D017311:Amlodipine; D020748:Mibefradil; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester