Central kappa opioid receptor-evoked changes in renal function in conscious rats: participation of renal nerves.

The present investigations examined the cardiovascular and renal responses produced by central nervous system stimulation of kappa opioid receptors by the selective kappa opioid receptor agonist, U-50488H, in conscious Sprague-Dawley rats. Administration of U-50488H (1 microgram total) into the lateral cerebroventricle produced a profound diuretic and antinatriuretic response. In addition, concurrent with the decrease in urinary sodium excretion, i.c.v. U-50488H elicited an increase in renal sympathetic nerve activity. The increases in urine flow rate and renal sympathetic nerve activity and the decrease in urinary sodium excretion produced by U-50488H were completely prevented in rats that had undergone pretreatment with the selective kappa opioid receptor antagonist, nor-binaltorphimine. In contrast, in animals that had undergone irreversible mu opioid receptor blockade with the selective mu opioid receptor antagonist, beta-funaltrexamine, central U-50488H administration elicited similar diuretic and antinatriuretic responses as observed in intact naive animals. In further studies, the antinatriuretic response produced by i.c.v. U-50488H was completely abolished in rats that had undergone chronic bilateral renal denervation, a technique used to remove the influence of the renal sympathetic nerves. Glomerular filtration rates and effective renal plasma flows were not altered by i.c.v. administration of U-50488H in intact or renal denervated animals. Together, these studies provide evidence for the role of central kappa opioid receptor mechanisms in the regulation of urinary sodium and water excretion. Moreover, these studies indicate that the changes in renal sodium handling produced by central kappa opioid agonists result from an action of these compounds to modulate sympathetic neural outflow to the kidneys.