The potassium channel opening action of pinacidil; studies using biochemical, ion flux and microelectrode techniques.
In rat aorta and rat portal vein, (-)- and (+)-pinacidil each produced a concentration-dependent inhibition of tension development. Although the (-) isomer was the more potent, concentration effect curves for each isomer were steep with similar slopes. In rat portal vein, tetraethylammonium and procaine antagonised the relaxant effect of (+/-)-pinacidil, whereas 3,4-diamino-pyridine was without effect. Intracellular microelectrode recording in rat portal vein showed that low concentrations of (+/-)-pinacidil reduced the duration of multispike electrical complexes. In both rat aorta and rat portal vein, higher concentrations of (+/-)-pinacidil hyperpolarised the membrane towards the potassium equilibrium potential. (+/-)-Pinacidil increased 86Rb efflux from rat aorta and rat portal vein in a concentration dependent manner. In a separate study, (+/-)-pinacidil increased 42K efflux from rat portal vein. (+/-)-Pinacidil had no effect on cyclic GMP or cyclic AMP levels in rat aorta. It is concluded that pinacidil opens 86Rb-permeable potassium channels in rat aorta and rat portal vein. This mechanism is independent of cyclic nucleotide changes and may be responsible for the antihypertensive effect of pinacidil.
Southerton
J S
JS
Department of Physiological Sciences, Medical School, University of Manchester, United Kingdom.
Weston
A H
AH
Bray
K M
KM
Newgreen
D T
DT
Taylor
S G
SG
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007536:Isomerism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D020110:Pinacidil; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000959:Antihypertensive Agents; D006146:Guanidines; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D020110:Pinacidil; D000242:Cyclic AMP; D006152:Cyclic GMP