Role of renal nerves in excretory responses to exogenous and endogenous opioid peptides.
The present study was designed to investigate opioid peptide-mediated changes in renal function in conscious Sprague-Dawley rats after administration of the native opioid agonist methionine enkephalin (ME), its synthetic analog D-Ala2-methionine enkephalinamide (DALA) and the opioid antagonist naloxone. Intravenous infusion of DALA (25 micrograms/kg/min) and ME (75 micrograms/kg/min) produced no changes in mean arterial pressure, heart rate, glomerular filtration rate or effective renal plasma flow in rats with intact or bilaterally denervated kidneys. In contrast, i.v. infusion of these opioid agonists produced differing effects on the renal excretion of water and sodium; DALA produced an increase in urinary flow rate and sodium excretion and ME produced a decrease in these parameters. Changes in renal sympathetic nerve activity were not involved in producing these effects as supported by measurements of renal sympathetic nerve activity and the finding that prior bilateral renal denervation did not alter the renal responses to either agonist. The renal excretory responses to both DALA and ME infusion were prevented by pretreatment with the opioid receptor antagonist naloxone, thus suggesting an opioid receptor-mediated effect of both agonists. Intravenous bolus injections of naloxone alone produced a dose-dependent diuresis and natriuresis without producing changes in systemic or renal hemodynamics or renal sympathetic nerve activity. These studies, therefore, provide evidence that the administration of opioid receptor agonists and antagonists produce changes in the renal excretion of water and sodium via an action on renal tubular reabsorptive mechanisms which are independent of changes in systemic or renal hemodynamics or renal sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Kapusta
D R
DR
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Jones
S Y
SY
Kopp
U C
UC
Dibona
G F
GF
D000818:Animals; D001834:Body Water / Q000378:metabolism; D003714:Denervation; D004723:Endorphins / Q000494:pharmacology* / Q000502:physiology; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D004723:Endorphins; D009270:Naloxone; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D012964:Sodium