Central mu opioid receptor-mediated changes in renal function in conscious rats.
Studies were performed in conscious Sprague-Dawley rats to determine whether the renal sympathetic nerves contribute to the renal excretory responses produced by central mu opioid agonist administration. Intracerebroventricular, but not i.v. injection of the selective mu opioid agonist dermorphin (0.1 nmol/kg), produced an increase in urine flow rate and a sustained decrease in urine sodium excretion. These renal excretory responses were completely prevented by pretreatment with the selective mu opioid antagonist, beta-funaltrexamine (20 micrograms, i.c.v.). Central dermorphin administration did not alter glomerular filtration rate or effective renal plasma flow. In contrast, efferent renal sympathetic nerve activity increased over the same time frame as the reduction in urinary sodium excretion. To investigate whether the dermorphin-induced antinatriuretic response was mediated via the increase in renal sympathetic nerve activity, experiments were repeated in Sprague-Dawley rats that had undergone chronic bilateral renal denervation. In renal denervated rats, i.c.v. dermorphin produced similar diuretic and antinatriuretic responses as were seen in rats with an intact renal innervation. Together, these studies indicate that the changes in urine flow rate and urinary sodium excretion produced by i.c.v. dermorphin were not mediated via central induced changes in renal hemodynamics or sympathetic outflow to the kidneys. Because an antinatriuretic response occurred in renal denervated animals, this suggests that central mu opioid receptor agonists may exert an influence on tubular reabsorption of sodium via mu opioid receptor-mediated mechanisms independent of intact renal innervation.
Kapusta
D R
DR
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans.
Obih
J C
JC
Dibona
G F
GF
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001834:Body Water / Q000378:metabolism; D003714:Denervation; D004333:Drug Administration Routes; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D018847:Opioid Peptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000652:urine; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D000701:Analgesics, Opioid; D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C030058:dermorphin; D012964:Sodium