Central alpha2-receptor mechanisms contribute to enhanced renal responses during ketamine-xylazine anesthesia.

We have recently developed an experimental approach to study central opioid control of renal function in anesthetized rats. This model system uses the intravenous infusion of the alpha2-agonist xylazine to enhance basal levels of urine flow rate and urinary sodium excretion in ketamine-anesthetized rats. This study examined the contribution of central and peripheral alpha2-adrenergic receptor mechanisms in mediating the enhanced renal excretory responses produced by xylazine. In ketamine-anesthetized rats, the enhanced levels of urine flow rate and urinary sodium excretion produced by the intravenous infusion of xylazine were reversed by the intravenous bolus injection of the alpha2-adrenoceptor antagonist yohimbine but not by the alpha1-adrenoceptor antagonist terazosin. In separate animals the intracerebroventricular administration of yohimbine only reduced urine flow rate by approximately 50% but did not alter urinary sodium excretion. The decrease in urine flow rate produced by intracerebroventricular yohimbine was reversed by the intravenous injection of a selective V2-vasopressin receptor antagonist. In a separate group of ketamine- and xylazine-anesthetized rats, the bilateral microinjection of yohimbine into the hypothalamic paraventricular nucleus (PVN) also significantly decreased urine flow rate by 54% without altering urinary sodium excretion. The microinjection of the beta-adrenoceptor antagonist propranolol into the PVN did not alter either renal excretory parameter. These results suggest that during intravenous infusion, xylazine increases urine flow rate by activating alpha2-adrenergic receptors in the PVN, which in turn decrease vasopressin release. The ability of alpha-adrenergic mechanisms in the PVN to selectively influence the renal handling of water, but not sodium, may contribute to the reported dissociation of the natriuretic and diuretic responses of alpha2-adrenoceptor agonists.