Antagonistic effects of atipamezole and yohimbine on medetomidine-induced diuresis in healthy dogs

Abstract

This study aimed to investigate and compare the antagonistic effects of atipamezole and yohimbine on medetomidine-induced diuresis in healthy dogs. Five dogs were used repeatedly in each of 8 groups. One group was not medicated. Dogs in the other groups received 20 microg/kg of medetomidine intramuscularly and, 0.5 h later, saline (as the control injection), 50, 100, or 300 microg/kg of atipamezole, or 50, 100, or 300 microg/kg of yohimbine intramuscularly. Urine and blood samples were taken 11 times over 24 h for measurement of the following: urine volume, specific gravity, and creatinine concentration; urine and plasma osmolality; urine and plasma concentrations of electrolytes and arginine vasopressin (AVP); and the plasma concentration of atrial natriuretic peptide (ANP). Both atipamezole and yohimbine antagonized the diuretic effect of medetomidine, inhibiting medetomidine-induced decreases in urine specific gravity, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and AVP and reversing both the medetomidine-induced increase in plasma concentrations of sodium, potassium, and chloride and the medetomidine-induced decrease in the plasma AVP concentration. Atipamezole significantly stimulated ANP release. The antidiuretic action of yohimbine was more potent than that of atipamezole but was not dose-dependent, in contrast to the action of atipamezole. The effects of these drugs may not be due only to actions mediated by alpha(2)-adrenoceptors.

Figure 1

Urine volume in 5 dogs before (0) and after intramuscular injection of physiological saline (Saline) or medetomidine followed, 0.5 h later, by saline again (MED) or by atipamezole (ATI) or yohimbine (YOH), the last 2 drugs in doses of 50, 100, or 300 μg/kg. A, B: Each point and vertical bar represent the mean and standard error (n = 5) of the rate of diuresis at various time points. The letters indicate a significant difference from the baseline (0) value (a — P < 0.05; b — P < 0.01) or from the value for the MED group (c — P < 0.05; d — P < 0.01). The points, bars, and letters have the same meanings in Figures 2 through 6. C, D: Simple linear regression of total urine volume in the period 0.5 to 4 h after the injection of medetomidine.

Figure 2

Urine specific gravity (A, B) and creatinine concentration (C, D) before and after injection of saline or medetomidine.

Figure 3

Osmolality of urine (A, B) and plasma (C, D) before and after injection of saline or medetomidine.

Figure 4

Total urine excretion of arginine vasopressin (AVP) between 0.5 and 4 h after the injection of saline or medetomidine. On the x axis, “50”, “100”, and “300” indicate the dose, in micrograms per kilogram, of the 2nd drug injected: atipamezole (A) or yohimbine (B); the same explanation applies in Figures 5 and 6.

Figure 5

The area under the curve (AUC) for the plasma AVP concentration between 0.5 and 2 h after the injection of saline or medetomidine.

Figure 6

Simple linear regression of the AUC data for the plasma concentration of atrial natriuretic peptide (ANP) between 0.5 and 4 h after the injection of saline or medetomidine.