The action of pinacidil in the isolated human bladder.
The need for effective symptomatic treatment of patients with detrusor hyperactivity is widely recognized. In search of new principles of decreasing bladder contraction we have studied the effects of pinacidil on the isolated human bladder. Pinacidil is a recently developed antihypertensive agent classified as a K+ channel opener, and is believed to depress smooth muscle activity by this action. Pinacidil concentration-dependently depressed contractions elicited by carbachol, low concentrations of K+ (less than 60 mM) and electrical stimulation. In addition it caused a concentration-related increase in the efflux of 86Rb from preloaded detrusor cells. The effects on 86Rb efflux could be inhibited by tetraethylammonium chloride and procaine, but not by apamin, agents known to block K+-channels. The results support the view that part of the pinacidil effect on the human bladder is caused by an opening of K+-channels, efflux of K+ and subsequent hyperpolarization of the detrusor cells. Clinical testing of this new therapeutic principle for treatment of bladder hyperactivity seems justified.
Fovaeus
M
M
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Andersson
K E
KE
Hedlund
H
H
D000959:Antihypertensive Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects*
D000959:Antihypertensive Agents; D006146:Guanidines; D015221:Potassium Channels; D020110:Pinacidil