MICROINJECTION OF THE KAPPA OPIOID RECEPTOR AGONIST U‐50448H INTO THE MEDIAL PREOPTIC AREA INCREASES RENAL SNA AND DECREASES SODIUM EXCRETION WITHOUT SIGNIFICANTLY IMPACTING CARDIOVASCULAR FUNCTION

Abstract

Intracerebroventricular (icv) injection of the kappa opioid agonist, U-50448H (U-50), produces a marked diuresis, antinatriuresis, and an increase in renal sympathetic nerve activity (RSNA) in rats. Because the median preoptic area (MPO) expresses high amount of cFos staining following icv microinjection of U50, we examined if MPO injection of U50 would produce similar effects on cardiovascular and renal function as well as RSNA. Methods Rats anesthetized with urethane-chloralose were instrumented to record arterial blood pressure (ABP), heart rate (HR) and RSNA. Catheters were placed in a femoral vein for drug delivery and infusion of isotonic saline (55 μl/min) and in the urinary bladder for urine collection. Urine was sampled during two 10 min control periods and during six 10 min period beginning 10 min after MPO injection of U-50 or vehicle. Results U-50 significantly increased RSNA (P<0.05) and caused antinatriuresis (P<0.05) without changing HR, mean ABP, or urine output. MPO injections of saline were without affect. Conclusion The ability of MPO injection of U-50 increase RSNA and decrease sodium excretion without effecting cardiovascular function raises the possibility that MPO neurons could be an important substrate through which drugs targeting Kappa opioid receptors could selectively facilitate sodium excretion in sodium retaining diseases such as salt-sensitive hypertension, hepatic cirrhosis and chronic heart failure. This work was supported by SC2 HL104639.