Inhibition of isolated rat and human detrusor muscle contraction by disopyramide.
1. The aim of this study was to investigate the effect of in vitro and in vivo disopyramide treatment on human and rat isolated detrusor muscle contractile response. Muscle strips were suspended in an organ bath chamber containing Kreb's solution at 37 degrees C aerated with 95% oxygen and 5% carbon dioxide. 2. Disopyramide antagonized significantly the contractile response of isolated human detrusor muscle to carbachol stimulation, shifting the concentration-response curve to the right in a parallel manner. The pA2 for competitive inhibition was estimated to be 6.4 with a slope of 0.64 for disopyramide. 3. Rat detrusor muscle contractile response to electrical field stimulation (EFS) was inhibited by 28% (P < 0.01) after in vitro administration of disopyramide (7.5 x 10(-6) M). Disopyramide had no effect on the atropine-resistant component of the response to EFS or on spontaneous contractions of isolated rat detrusor muscle strips. The concentration-response curve to carbachol was competitively antagonized by disopyramide with a pA2 of 6.3 and a Schild curve a slope of 0.85. 4. Disopyramide (7.5 x 10(-6) M) had no effect on rat detrusor contractile response to low concentrations of KCl but at high concentrations contraction was reduced significantly by 16% (P < 0.01). 5. In vivo treatment of rats with disopyramide for 8 days or with a single dose had a significant inhibitory effect on the contractile response of detrusor muscle strips. 6. In conclusion, disopyramide had a significant anticholinergic effect on isolated human and rat detrusor muscle contraction.
University of Leicester, Division of Medicine for the Elderly, Leicester General Hospital, UK.
R A
RA
Elliott
D
D
Hudman
T
T
Terry
D
D
Sandhu
R I
RI
Norman
D000368:Aged; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004206:Disopyramide / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D001285:Atropine; D002217:Carbachol; D004206:Disopyramide; D011188:Potassium