RT Journal Article
SR Electronic
T1 Central kappa opioids blunt the renal excretory responses to volume expansion by a renal nerve-dependent mechanism.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 199
OP 205
VO 273
IS 1
A1 D R Kapusta
A1 J C Obih
YR 1995
UL http://jpet.aspetjournals.org/content/273/1/199.abstract
AB Central administration of kappa opioids produce significant alteration in the renal excretion of sodium and water under basal conditions. To determine whether enhanced central kappa opioid activity alters the renal handling of sodium and water to an integrated physiological stimuli, we compared the renal excretory responses produced by acute i.v. isotonic saline volume expansion in conscious Sprague-Dawley rats pretreated with i.c.v. isotonic saline vehicle or the selective kappa opioid agonist, U-50488H. In vehicle-treated animals, isotonic saline volume expansion produce an increase in urine flow rate and urinary sodium excretion and a decrease in efferent renal sympathetic nerve activity. In comparison with these control responses, isotonic saline volume expansion produced a similar magnitude change in urine flow rate in rats pretreated i.c.v. with U-50488H. In contrast, the natriuretic response produced by the isotonic saline load was markedly blunted in these central kappa opioid-treated animals. Moreover, the sympathoinhibitory response characteristically produced by the isotonic saline volume expansion was completely prevented in animals receiving i.c.v. U-50488H. To elucidate further the role of the renal nerves in mediating this central kappa opioid-induced renal excretory response, these studies were repeated in chronic bilaterally renal denervated rats. The results of these studies demonstrated that bilateral renal denervation restored the capacity of i.c.v. U-50488H-pretreated rats to maximally excrete the sodium load. Together, these studies demonstrate that, in conscious Sprague-Dawley rats, increased central kappa opioid activity significantly blunts the natriuretic response to isotonic saline volume expansion by a renal nerve-dependent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)