DRUGS ACTING ON CALCIUM CHANNELS MODULATE THE DIURETIC AND MICTURITION EFFECTS OF DEXMEDETOMIDINE IN RATS

The purpose of this study was to assess the effects of calcium channel antagonist, verapamil, and agonist, Bay K 8644. on the alpha(2)-adren oceptor agonist, dexmedetomidine-induced (300 mu g kg(-1) subcutaneous ly) diuresis and overflow incontinence, in rats. Ultrasonography study revealed that verapamil (2.5 mg kg(-1) subcutaneously) or Bay K 8644 (0.5 mg kg(-1) intraperitoneally) coadministrations delayed dexmedetom idine-induced bladder filling and significantly prolonged the latency of urination (P<0.05). Bay K 8644 decreased relative bladder volume an d stopped continuous urination from dexmedetomidine, whereas verapamil had neither effect. However, none of the drugs eliminated the overflo w incontinence. Dexmedetomidine alone increased the hourly and total ( for 4 hours) urine volume. Bay K 8644 (0.5 or 1 mg kg(-1)) dose-depend ently decreased the diuretic effect of dexmedetomidine (P<0.001). Vera pamil (0.5, 1 or 2.5 mg kg(-1)) dose-dependently decreased urine volum e in the first hour (P<0.01), and thereafter potentiated the diuretic effect of dexmedetomidine. Simultaneous determinations of mean arteria l blood pressure (MAP) and urine output after dexmedetomidine and the highest dose of verapamil coadministration demonstrated a significant correlation between these variables (r=0.537; P<0.001). MAP of 100 mmH g or less was associated with a urine output significantly lower (P<0. 001) than that at higher pressures. Thus, hypotension during the first hour after dexmedetomidine-verapamil may explain the transient reduct ion in urination during this period. We conclude that modulation of ca lcium channels affects dexmedetomidine actions on both urine formation and micturition. Since both alpha(2)-adrenoceptor agonists and calciu m channel blockers have frequently been used for antihypertensive ther apy and as adjuvant drugs during anesthesia, these interactions may ha ve some practical importance.