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  • Title: Calcium channel blockade in smooth muscle of the human upper urinary tract. I. Effects on depolarization-induced activation.
    Author: Hertle L, Nawrath H.
    Journal: J Urol; 1984 Dec; 132(6):1265-9. PubMed ID: 6094847.
    Abstract:
    The effects of the calcium blockers nifedipine, verapamil, D600 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 potassium-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 potassium concentration induced contractions concentration-dependently. A log-linear relationship between the extracellular calcium concentration and the 85 mmol./l. potassium-induced activation was demonstrated. Concentration-response relationships of the compounds were found by activating the muscle strips with 85 mmol./l. potassium 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 value; its relative potency with reference to papaverine was about 8,000 to 1. The order of potency of the other drugs was in the following sequence: D600 greater than verapamil greater than diltiazem. It is concluded that processes in the human upper urinary tract which are triggered by depolarization (action potential or high potassium concentrations) are highly sensitive to calcium channel blockers.
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