Renal actions of the alpha2-adrenoceptor agonist, xylazine, in the anaesthetised rat

AIMS: The aims of the present study were to characterise the renal effects of the alpha2-adrenergic agonist, xylazine, in the rat and to test the role of changes in glomerular filtration rate, glucosuria, and arginine vasopressin (AVP) in its mechanism of action. METHODS: Male Wistar rats were anaesthetised with pentobarbitone sodium (50 mg/kg), and polyethylene cannulae were surgically placed for blood pressure measurement and for blood and urine collection. Rats were given xylazine and other alpha2 agonists by bolus intravenous dose, and the effects of the drugs were monitored in the presence and absence of the selective alpha2 antagonist, yohimbine, the alpha1, alpha2B antagonist, prazosin, and the V2-receptor antagonist, d(CH2)5 [D-Ile2,Ile4,Ala-NH29]AVP. RESULTS: Xylazine at 2.5 mg/kg caused a significant and prolonged dose-dependent increase in urine flow rate and sodium excretion but had only short-lasting effects on blood pressure, heart rate, and glomerular filtration rate. Prazosin had no effect on the measured responses. Although plasma glucose concentration and glucose excretion rate were increased by xylazine, the magnitudes of these increases were insufficient to account for the diuresis observed. Xylazine, and 2 other alpha2 agonists, clonidine and oxymetazoline, increased urine flow and/or sodium excretion despite the presence of d(CH2)5 [D-Ile2,Ile4,Ala-NH29]AVP. CONCLUSIONS: Xylazine causes a diuretic and natriuretic alpha2A-adrenergic response in the rat that is independent of changes in glomerular filtration rate, the development of glucosuria, or AVP action on the distal nephron of the kidney. CLINICAL RELEVANCE: The adverse effects of xylazine on salt and water balance need to be considered and possibly compensated for by fluid replacement or post-surgical administration of alpha2-receptor antagonists.