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2015 ; 3
(2
): e00117
Nephropedia Template TP
gab.com Text
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English Wikipedia
Renal responses produced by microinjection of the kappa opioid receptor agonist,
U50-488H, into sites within the rat lamina terminalis
#MMPMID26038693
Franklin C
; Fortepiani L
; Nguyen T
; Rangel Y
; Strong R
; Gottlieb HB
Pharmacol Res Perspect
2015[Mar]; 3
(2
): e00117
PMID26038693
show ga
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 ?L/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 ?L/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.