Calcium Channel Blockade in Smooth Muscle of The Human Upper Urinary Tract. I. Effects on Depolarization-Induced Activation

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Abstract
The effects of the Ca blockers nifedipine, verapamil, D600 [methoxyverapamil] and diltiazem on mechanical activity were studied in isolated preparations of the human upper urinary tract. Two types of activity were used: spontaneous phasic-rhythmic activity in calyceal segments, and K-induced depolarization in ureteral muscle strips. Nifedipine (10-6 mol/l), verapamil, D600 and diltiazem (all 10-5 mol/l) completely suppressed spontaneous phasic-rhythmic activity. Elevation of extracellular K concentration induced contractions concentration-dependently. A log-linear relationship between the extracellular Ca concentration and the 85 mmol/l K-induced activation was demonstrated. Concentration-response relationships of the compounds were found by activating the muscle strips with 85 mmol/l K in the Tyrode solution. This activation model produced stable and reproducible contractures. The compounds antagonized depolarization-induced activations concentration-dependently, nifedipine being the drug with the lowest EC50 [median effective concentration] value; its relative potency with reference to papaverine was .apprx. 8000 to 1. The order of potency of the other drugs was in the following sequence: D600 > verapamil > diltiazem. Processes in the human upper urinary tract which are triggered by depolarization (action potential or high K concentrations) are highly sensitive to Ca channel blockers.