Vol. 282, Issue 2, 609-616, 1997

Renal Excretory Responses Produced by Central Administration of Opioid Agonists in Ketamine and Xylazine-Anesthetized Rats¹

Antonio M. Cabral, Kurt J. Varner and Daniel R. Kapusta

Department of Physiological Sciences, Federal University of Espirito Santo, Brazil (A.-M.C.) and the Department of Pharmacology and Experimental Therapeutics (K.J.V., D.R.K.), Louisiana State University Medical Center, New Orleans, Louisiana

This study examined the renal excretory responses produced by the intravenous (i.v.) infusion of the alpha-2 agonist, xylazine, in ketamine-anesthetized rats. In addition, the renal responses produced by the intracerebroventricular (i.c.v.) injection of opioid agonists were also examined with use of this anesthetic paradigm. In male Sprague-Dawley rats, the i.v. infusion of isotonic saline (55 µl/min) containing ketamine alone (1.0 mg/kg/min) produced low levels of urine flow rate (6.3 ± 1.3 µl/min/gkw) and urinary sodium excretion (0.28 ± 0.08 µeq/min/gkw). However, after adding xylazine (50 µg/kg/min) to the ketamine infusate, these renal excretory responses were significantly augmented. Steady-state levels of urine flow rate and urinary sodium excretion were attained approximately 120 min after starting the xylazine infusion and were similar in magnitude to the levels of water and sodium excretion previously observed in untreated, conscious rats. In ketamine/xylazine-anesthetized rats, the i.c.v. injection of the mu opioid agonist, dermorphin (0.1 nmol/kg), or the kappa opioid agonist, U-50488H (1 µg total), produced profound and concurrent diuretic and antinatriuretic responses. The pattern (direction and magnitude) of these opioid-induced renal excretory responses was similar to those previously reported in conscious rats. Together, these results indicate that the i.v. infusion of xylazine enhances the renal excretion of water and sodium in ketamine-anesthetized rats. Moreover, the renal responses produced by i.c.v. administration of opioids are similar in ketamine/xylazine-anesthetized and conscious rats. Thus, it appears that the ketamine/xylazine infusion protocol may provide a valid and useful approach to investigate various aspects of the central opioid control of renal function in rats during experimental procedures that require anesthesia.