Effects of pinacidil on bladder muscle.
Infravesical outflow obstruction and bladder hypertrophy are often associated with bladder hyperactivity causing frequency, urge and urinary incontinence. This hyperactivity may be due to a supersensitivity to depolarising stimuli. Drugs that inhibit smooth muscle activity by opening K+ channels, resulting in hyperpolarisation, would therefore seem to be an attractive therapeutic principle. Pinacidil is an effective vasodilator classified as a K+ channel opener. The drug has been shown to effectively depress spontaneous contractile activity, the contractions induced by low (less than 40 mmol/L) concentrations of K+, carbachol and by electrical stimulation of nerves in isolated normal human bladder tissue and also in normal and hypertrophied rat bladder. The effect was more pronounced in hypertrophied detrusor. Pinacidil in concentrations inhibiting muscle activity also increased the efflux of 86Rb in bladder tissue. In vivo pinacidil suppressed spontaneous contractile activity in rats with infravesical bladder obstruction and detrusor hypertrophy. The findings make K+ channel openers an interesting, potentially useful therapeutic principle in hyperactivity associated with bladder hypertrophy.
Andersson
K E
KE
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Andersson
P O
PO
Fovaeus
M
M
Hedlund
H
H
Malmgren
A
A
Sjögren
C
C
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; 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