Positive inotropic actions of the calcium channel stimulator, Bay k 8644, in awake, unsedated dogs.
The hemodynamic effects of the dihydropyridine derivative Bay k 8644, a new calcium agonist with positive inotropic actions, were studied in instrumented conscious dogs before and after beta adrenergic blockade with propranolol. Intravenous Bay k 8644 (2, 4, 8 and 20 micrograms/kg/min) produced dose-related increases in arterial and left ventricular systolic pressures and myocardial contractility (+dP/dt; % segment shortening). Coronary blood flow velocity was increased at higher doses. Prior administration of propranolol produced no significant alteration of the hemodynamic effects of Bay k 8644. Increases in arterial and left ventricular pressures produced by Bay k 8644 were controlled by intravenous infusion of sodium nitroprusside with resulting enhancement of positive inotropic effects. The results demonstrate that the hemodynamic responses to this novel calcium agonist with positive inotropic properties are not mediated via beta adrenergic mechanisms and control of increases in arterial pressure lead to enhanced regional contractility.
Preuss
K C
KC
Brooks
H L
HL
Gross
G J
GJ
Warltier
D C
DC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D007473:Ion Channels; D011943:Receptors, Adrenergic, beta; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011433:Propranolol; D009543:Nifedipine; D002118:Calcium