Renal responses produced by microinjection of the kappa opioid receptor agonist, U50-488H, into sites within the rat lamina terminalis

Activation of central kappa opioid receptors (KOR) has been demonstrated to produce marked free water diuresis with a concurrent increase in renal sympathetic nerve activity (RSNA). This study investigated the cardiovascular (CV) and renal effects evoked by central activation of KOR in two lamina terminalis sites, the median preoptic area (MPA) and anterolateral division of the bed nuclei of the stria terminalis (BST). Rats anesthetized with urethane alpha-chloralose were instrumented to record mean arterial pressure, heart rate, RSNA, and urine output (V). Rats were infused with isotonic saline (25 μL/min) and urine samples were collected during two 10-min control periods and six consecutive 10-min experimental periods following microinjection of vehicle, U50-448H (U50, KOR agonist) alone or norbinaltorphimine (nor-BNI, KOR antagonist) plus U50. Microinjection of U50 into the BST increased V (peak at 30 min, 84.8 ± 12.9 μL/min) as compared to its respective control, vehicle, or nor-BNI plus U50. This diuretic effect occurred without any significant changes in CV parameters, RSNA, or urinary sodium excretion. In contrast, U50 injection into the MPA significantly increased RSNA (peak at 20 mins: 129 ± 9.9) without increasing the other parameters. This study demonstrated novel sites through which activation of KOR selectively increases V and RSNA. The ability of U50 to increase V without affecting sodium excretion and RSNA raises the possibility that LT neurons could be an important substrate through which drugs targeting KOR could selectively facilitate water excretion in sodium-retaining diseases such as congestive heart failure.