Effects of vatinoxan and fentanyl on blood glucose concentrations and diuresis in male Wistar rats sedated with medetomidine and midazolam

BACKGROUND: Alpha2-adrenoceptor agonists such as medetomidine induce hyperglycemia, glucosuria, and polyuria. We evaluated the ability of vatinoxan, a peripherally acting alpha2-adrenoceptor antagonist, to mitigate these side effects in male Wistar rats (N = 31). To explore its impact on two common sedation protocols in laboratory rats, a randomized, controlled experimental study was conducted comprising four groups: medetomidine (0.25 mg/kg) and midazolam (2.0 mg/kg) (MM; N = 8), MM + fentanyl (0.01 mg/kg) (MMF; N = 8), MM vatinoxan (MMV; N = 7), and MMF + vatinoxan (MMFV; N = 8). Blood glucose concentration (BG) was measured repeatedly between 10 and 60 min after treatment administration, and total urine output and body weight change were assessed. Additionally, urine glucose concentration (UG) was measured at 45 and 75 min. RESULTS: Pooled BG was significantly higher in non-vatinoxan treated rats [19.8 ± 3.6 mmol/L (mean ± SD) with MM + MMF compared with 10.3 ± 1.2 mmol/L with MMV + MMFV] (P < 0.001). Similarly, urine output was greater without vatinoxan [median 22.9 (minimum–maximum) 10.6–32.9) vs. 2.8 (0.0–7.4) ml/kg/h] (P < 0.001). Vatinoxan also reduced UG [33.3 (0.6–33.3) vs. 1.4 (0.9–3.2) mmol/L] (P < 0.01) and body weight loss. Fentanyl did not significantly alter these outcomes. Rats were sufficiently sedated after all treatments. CONCLUSIONS: The findings demonstrate that vatinoxan effectively mitigates hyperglycemia, polyuria and glucosuria induced by medetomidine-based sedation protocols in adult, male Wistar rats.