The hemodynamic effects of lacidipine in anesthetized dogs: comparison with nitrendipine, amlodipine, verapamil, and diltiazem.
The hemodynamic effects of lacidipine in anesthetized, open-chest dogs were compared with those of nitrendipine, amlodipine, verapamil and diltiazem. Lacidipine administered intravenously induced dose-related, long-lasting reductions in systemic and coronary vascular resistance with corresponding increases in aortic flow and coronary blood flow. The hypotensive effect (ED25 for mean blood pressure reduction = 0.006 mg/kg) was still significant 120 min after administration with all doses tested. Nitrendipine was equipotent with lacidipine in reducing the mean blood pressure (ED25 = 0.005 mg/kg), but its effect was shorter acting (significant effect at 120 min only with the highest dose tested). Amlodipine caused a marked and long-lasting hypotension though at higher doses than lacidipine (ED25 = 0.50 mg/kg). Short-lasting hypotensive responses were also detected with verapamil (ED25 = 0.1 mg/kg) and diltiazem (ED25 = 0.12 mg/kg). A reflex increase in heart rate was observed with lacidipine, nitrendipine, and amlodipine, whereas verapamil and diltiazem showed a dose-related bradycardia. No effect on AV conduction was observed with lacidipine and nitrendipine, whereas amlodipine, verapamil, and diltiazem produced second- to third-degree AV block at the highest doses tested. Lacidipine and nitrendipine caused a reflex increase in contractile index at all doses, whereas amlodipine was more similar to verapamil since a marked decrease in contractile index was detected at the highest dose. Diltiazem was practically devoid of negative inotropic effect.
Quartaroli
M
M
Glaxo Research Laboratories, Verona, Italy.
Gambini
F
F
Tarter
G
G
Micheli
D
D
Trist
D G
DG
Gaviraghi
G
G
D017311:Amlodipine; D000758:Anesthesia; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; C060285:lacidipine; D009568:Nitrendipine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine