Renal effects produced by microinjection of kappa opioid agonist into the bed nuclei of the stria terminalis (BST)

Abstract

Intracerebroventricular (ICV) injection of the kappa opioid agonist, U‐50448H (U50), produces a marked diuresis, antinatriuresis, and an increase in renal sympathetic nerve activity (RSNA). The dorsomedial BST has been show to express kappa opioid receptors (KOR) that project to the hypothalamic areas involved in water homeostasis, therefore we examined if injection of U50 into the BST would produce similar effects on renal function.MethodsRats 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 (25 μl/min) and in the urinary bladder for urine collection. Urine was sampled during two 10 min control and six 10 min periods starting 10 min after injection of U50 or vehicle to the BST.ResultsU50 significantly increased urine excretion (n=8, P<0.05) without changing HR, mean ABP, urinary sodium excretion or RSNA. Injections of saline (n=8) were without affect.ConclusionThe ability of U50 to increase urine outflow without effecting sodium excretion and RSNA raises the possibility that BST neurons could be an important substrate through which drugs targeting Kappa opioid receptors could selectively facilitate water excretion in sodium retaining diseases such as salt‐sensitive hypertension. This work was supported by 5SC2 HL104639.