Inhibitory effects of various L-type and T-type calcium antagonists on electrically generated, potassium-induced and carbachol-induced contractions of porcine detrusor muscle.
The inhibitory effects of different calcium antagonists on contractions of isolated porcine detrusor muscle were investigated. Suppression of the maximum potassium-induced contraction and electrically generated contractions by nifedipine, verapamil and diltiazem were investigated. Furthermore, concentration-response curves of carbachol after pretreatment with the L-type antagonists nifedipine, verapamil, diltiazem, nimodipine and the T-type antagonist mibefradil at different concentrations were performed. Nifedipine significantly reduced the potassium-induced maximum contraction to 89, 60, 21, 8 and 4% (10(-9)-10(-5) M). Verapamil and diltiazem significantly reduced it to 64, 30 and 5% (10(-7)-10(-5) M) or 79, 27, 7 and 1% (10(-7)-10(-4) M), respectively. Nifedipine, verapamil and diltiazem significantly reduced the electrically generated contraction to 55, 36, 34 and 25% (10(-7)-10(-4) M), 71, 32 and 2% (10(-6)-10(-4) M), 96, 78, 38 and 5% (10(-7)-10(-4) M), respectively. pD2 values of nifedipine, verapamil and diltiazem amounted to 7.07, 5.56 and 5.40 and differed significantly. After pretreatment with nifedipine at 10(-6) M, the concentration-response curve of carbachol was nearly suppressed. The effects of nimodipine, verapamil and diltiazem were smaller. Mibefradil caused only at 10(-5) M a significant reduction. All investigated L-type calcium antagonists were strong inhibitors of the examined contractions. Nifedipine showed the biggest inhibitory effect.
Badawi
Jasmin Katrin
JK
Department of Urology, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. jasmin-katrin.badawi@uro.ma.uni-heidelberg.de
Li
Heng
H
Langbein
Sigrun
S
Kamp
Stefan
S
Guzman
Sergio
S
Bross
Stephan
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D018678:Cholinergic Agents; D002217:Carbachol; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium