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-adrenoceptor agonist, dexmedetomidine-induced (300 micrograms 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 < 0.01). 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 channel affects dexmedetomidine actions on both urine formation and micturition. Since both alpha 2-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.
Horváth
G
G
Department of Physiology and Radiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Morvay
Z
Z
Kovács
M
M
Szilágyi
A
A
Szikszay
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D051381:Rats; D017208:Rats, Wistar; D014463:Ultrasonography; D001743:Urinary Bladder / Q000000981:diagnostic imaging / Q000502:physiology; D014554:Urination / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D007093:Imidazoles; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D020926:Medetomidine