[Potassium channel activators. Perspectives in the treatment of arterial hypertension].
Potassium channel activators (PCAs) open the membrane potassium channels, thus increasing the cell potassium efflux. This results in hyperpolarization of the cell membrane, the main result of which is a reduction of the penetration of calcium into cells. The resulting decrease of intracellular Ca++ produces relaxation of the smooth muscle fibres, notably in blood vessels. In animals, PCAs reduce total peripheral resistance and lower blood pressure. These vasodilator and hypotensive effects are accompanied by reflex tachycardia and stimulation of the renin-angiotensin system and they are antagonized by glibenclamide, an antagonist of ATP-dependent potassium channels. Very recent experimental data have shown that in the ischaemic myocardium PCAs tend to improve the balance between oxygen supply and demand and to exert a cardioprotective effect. Up to now, the only use of PCAs has been in arterial hypertension, and the only drugs used are pinacidil, minoxidil and diazoxide. Unfortunately, the PCAs that are available at present are rather poorly tolerated, which limits their development in this particular field. However, their combination with beta-blockers and/or diuretics reduces the incidence of their side-effects and improves their effectiveness. A synergistic effect between PCAs and angiotensin-converting enzyme inhibitors is probable.
Giudicelli
J F
JF
Département de pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicetre.
Richer
C
C
Berdeaux
A
A
D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D019806:Cromakalim; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use
D000959:Antihypertensive Agents; D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D020110:Pinacidil
Les activateurs des canaux potassiques. Perspectives dans le traitement de l'hypertension artérielle.