The action of amlodipine on human subcutaneous resistance arteries studied in vitro.
The effect of amlodipine, a dihydropyridine calcium antagonist which is largely ionized at physiological pH, was studied in human resistance arteries. Resistance arteries were isolated from subcutaneous fat and isometric force measured in a myograph. Amlodipine inhibited depolarization-induced contractions in a time- and concentration-dependent manner. The potency of amlodipine was markedly increased by depolarization of the resistance arteries by a physiological saline containing high potassium (40 mM) during exposure to amlodipine. The onset and offset of amlodipine-induced inhibition in these arteries was slow, but concentration dependent. Depolarization markedly increased the rate of onset of inhibition. The increase in potency of amlodipine under depolarized conditions could largely be accounted for by the increased rate of association of the drug. Possible use-dependence of amlodipine was also examined in comparison with verapamil. The efficacy of both verapamil and amlodipine was increased in vessels which were repeatedly depolarized compared with vessels which were only activated once. This effect was more marked for verapamil than for amlodipine. The action of amlodipine in human resistance arteries is slow, shows marked voltage-dependence and, to a lesser degree, some use-dependence. These properties may be important in understanding the action of amlodipine in vivo.
Garcha
R S
RS
Department of Clinical Pharmacology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, England.
Sever
P S
PS
Hughes
A D
AD
D017311:Amlodipine / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D014655:Vascular Resistance / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D017311:Amlodipine; D014700:Verapamil