title: Vasodilatory action of amlodipine on rat aorta, pig coronary artery, human coronary artery, and on isolated Langendorff rat heart preparations.
abstract: Amlodipine inhibited contractions of rat aortic rings induced by 40 mM KCl (IC50 = 7.5 x 10(-9) M). The time to attain the maximum inhibitory effect of KCl-induced contractions was long (hours) and dependent on the concentration of amlodipine. After 6 h of washing in drug-free normal Krebs-Ringer solution the contractions recovered only partially. The KCl-induced contractions appeared to be more sensitive to inhibition by amlodipine than were norepinephrine-induced contractions. CaCl2-induced contraction of KCl-depolarized aortic rings was inhibited by amlodipine in a complex manner. Amlodipine not only increased ED50 but also inhibited the maximal tension induced by CaCl2. Amlodipine also inhibited 35 mM KCl-induced contractions of pig coronary artery rings (IC50 = 2.2 x 10(-8) M) and human coronary artery rings (IC50 = 2.1 x 10(-8) M). In Langendorff rat heart preparations, low concentrations of amlodipine increased coronary flow (ED50, 10(-9) M) whereas higher concentrations (greater than 10(-7) M) decreased coronary flow. Amlodipine also decreased the rate of contraction (+ dP/dt, IC50 = 3 x 10(-7) M) and the rate of relaxation (-dP/dt, IC50 = 1.2 x 10(-7) M). Amlodipine decreased heart rate but only at high concentrations (greater than 300 nM). The results of this study indicate that amlodipine is a potent vasodilator with similar cardiovascular actions to other dihydropyridines except that its effects are slower in onset and longer lasting.
authors: Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Ohio.
authors: M A
authors: MA
authors: Matlib
authors: J F
authors: JF
authors: French
authors: I L
authors: IL
authors: Grupp
authors: C
authors: C
authors: Van Gorp
authors: G
authors: G
authors: Grupp
authors: A
authors: A
authors: Schwartz
mesh_terms: D017311:Amlodipine; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013045:Species Specificity; D013552:Swine; D014665:Vasodilator Agents
chemical_list: D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D017311:Amlodipine; D009543:Nifedipine