Central alpha(2)-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 alpha(2)-agonist xylazine to enhance basal lev els of urine flow rate and urinary sodium excretion in ketamine-anesthetize d rats. This study examined the contribution of central and peripheral alph a(2)-adrenergic receptor mechanisms in mediating the enhanced renal excreto ry responses produced by xylazine. In ketamine-anesthetized rats, the enhan ced levels of urine flow rate and urinary sodium excretion produced by the intravenous infusion of xylazine were reversed by the intravenous bolus inj ection of the alpha(2)-adrenoceptor antagonist yohimbine but not by the alp ha(1)-adrenoceptor antagonist terazosin. In separate animals the intracereb roventricular administration of yohimbine only reduced urine flow rate by s imilar to 50% but did not alter urinary sodium excretion. The decrease in u rine flow rate produced by intracerebroventricular yohimbine was reversed b y the intravenous injection of a selective V-2-vasopressin receptor antagon ist. In a separate group of ketamine- and xylazine-anesthetized rats, the b ilateral microinjection of yohimbine into the hypothalamic paraventricular nucleus (PVN) also significantly decreased urine flow rate by 54% without a ltering urinary sodium excretion. The microinjection of the beta-adrenocept or antagonist propranolol into the PVN did not alter either renal excretory parameter. These results suggest that during intravenous infusion, xylazin e increases urine how rate by activating alpha(2)-adrenergic receptors in t he PVN, which in turn decrease vasopressin release. The ability of alpha-ad renergic mechanisms in the PVN to selectively influence the renal handling of water, but not sodium, may contribute to the reported dissociation of th e natriuretic and diuretic responses of alpha(2)-adrenoceptor agonists.