Effect of treatment with calcium antagonists in vitro and in vivo on the contractile response of isolated rat and human detrusor muscle.
1. The effect of calcium antagonists on the contractile response of human and rat isolated detrusor muscle in vitro was investigated. The effect of treatment with nimodipine on rat detrusor muscle in vivo was also examined. 2. Nimodipine 0.1 mumol/l, nifedipine 0.1 mumol/l, nifedipine 0.25 mumol/l and verapamil 1.5 mumol/l reduced the maximum contractile response of isolated human detrusor muscle to carbachol by 42%, 35%, 41% and 28% respectively (P < 0.01). Verapamil 0.1 mumol/l had no significant effect on contractile response. 3. Nimodipine 0.1 mumol/l reduced the maximum contractile response of isolated rat detrusor muscle in vitro to electrical field stimulation and carbachol by 53% and 84% respectively (P < 0.01). 4. Rats were pretreated with nimodipine for 8 days (5 mg day-1 kg-1) or with a single dose. Serum nimodipine concentrations were higher in rats treated for 8 days. In rats treated with nimodipine for 8 days there was no significant difference in detrusor contractile response compared with controls. However, after one dose of nimodipine the maximum contractile response was significantly reduced compared with controls (P < 0.05). 5. At the concentrations studied, nimodipine had a greater inhibitory effect on the contractile response of isolated human detrusor muscle. Nimodipine significantly reduced the contractile response of rat detrusor muscle in vitro and after a single dose in vivo, but had no significant effect after 8 days' treatment in vivo. It is possible that chronic oral treatment with nimodipine caused an up-regulation of 1,4-dihydropyridine-sensitive calcium channels, which may explain the lack of clinical effect of chronic treatment with calcium antagonists in patients with detrusor instability.
Elliott
R A
RA
Division of Medicine for the Elderly, University of Leicester, U.K.
Norman
R I
RI
Parker
S G
SG
Whitaker
R P
RP
Castleden
C M
CM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects; D014555:Urination Disorders / Q000503:physiopathology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009553:Nimodipine; D002217:Carbachol; D014700:Verapamil; D009543:Nifedipine