Renal mu opioid receptor mechanisms in regulation of renal function in rats

Studies were performed in pentobarbital anesthetized Sprague-Dawley rats to determine whether mu opioid receptor agonists produce changes in renal function via intrarenal mechanisms. Left renal artery infusion of isotonic saline vehicle or the selective mu opioid receptor agonist, dermorphin (0.5 nmol/kg/min), did not alter mean arterial pressure or heart rate. In contrast, left renal artery dermorphin administration produced a significant decrease in left kidney urinary flow rate and sodium excretion without altering glomerular filtration rate or effective renal plasma flow; function of the right kidney was unaffected. Pretreatment of the left kidney with the opioid receptor antagonist naloxone, 50 micrograms/kg into left renal artery, prevented changes in urinary flow rate and sodium excretion induced by subsequent left renal artery dermorphin administration. Prior bilateral renal denervation abolished the antidiuretic and antinatriuretic responses to left renal artery dermorphin administration. These results suggest that mu opioid receptor agonists participate in the process of renal tubular sodium and water reabsorption via an intrarenal action that is dependent on an interaction with renal sympathetic nerves. This may occur via an action of mu opioid receptor agonists to facilitate the nerve terminal release and/or the direct tubular action of norepinephrine to affect renal tubular sodium and water reabsorption.