The effects of racemic, (+)- and (-)-pinacidil on the membrane potential of the rat aorta.
The endothelium-intact and -denuded rat aorta is hyperpolarized by racemic and (-)-pinacidil, probably by opening ATP-dependent potassium channels. (+)-Pinacidil caused depolarization of the endothelium-intact and -denuded rat aorta. The depolarization induced by 20 mAM KCl in the endothelium-intact rat aorta was reversed by racemic and (-)-, but not by (+)-pinacidil. On the endothelium-intact rat aorta, isoprenaline produced hyperpolarization and ICI 118551 (erythro-(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylamino butan-2-ol) had no effect alone but prevented isoprenaline from causing hyperpolarization. The hyperpolarization induced by isoprenaline was reversed by racemic and (+)-, but not by (-)-pinacidil. Glibenclamide depolarized the endothelium-intact rat aorta and prevented the hyperpolarizing action of racemic pinacidil and (-)-pinacidil. (+)-Pinacidil prevented the hyperpolarizing action of (-)-pinacidil. Glibenclamide is probably preventing the hyperpolarization associated with opening of the ATP-dependent potassium channel by blocking this channel. Several mechanisms may underlie the depolarizing action of (+)-pinacidil, including blocking of ATP-dependent potassium channels.
Doggrell
S A
SA
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
Bishop
B E
BE
Barnett
C W
CW
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D020110:Pinacidil; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D011412:Propanolamines; D014665:Vasodilator Agents; C026777:ICI 118551; D020110:Pinacidil; D007545:Isoproterenol; D005905:Glyburide