The purpose of this study was to assess the effects of calcium channel antagonist, verapamil, and agonist, Bay K 8644, on the α2-adrenoceptor agonist, dexmedetomidine-induced (300 μg kg-1 subcutaneously) 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 dexmedetomidine-induced bladder filling and significantly prolonged the latency of urination (P<0.05). Bay K 8644 decreased relative bladder volume and stopped continuous urination from dexmedetomidine, whereas verapamil had neither effect. However, none of the drugs eliminated the overflow incontinence. Dexmedetomidine alone increased the hourly and total (for 4 hours) urine volume. Bay K 8644 (0.5 or 1 mg kg-1) dose-dependently decreased the diuretic effect of dexmedetomidine (P<0.001). Verapamil (0.5, 1 or 2.5 mg kg-1) dose-dependently decreased urine volume in the first hour (P<0.01), and thereafter potentiated the diuretic effect of dexmedetomidine. Simultaneous determinations of mean arterial 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 mmHg 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 reduction in urination during this period. We conclude that modulation of calcium channels affects dexmedetomidine actions on both urine formation and micturition. Since both α2-adrenoceptor agonists and calcium channel blockers have frequently been used for antihypertensive therapy and as adjuvant drugs during anesthesia, these interactions may have some practical importance.
- Bay K 8644
- alpha adrenoceptor agonist
- calcium channel agonist
- urinary bladder
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)