Central mu opioid receptor-mediated changes in renal function in conscious rats

Area of Science:

• Pharmacology
• Nephrology
• Neuroscience

Background:

• The role of renal sympathetic nerves in mediating central opioid effects on kidney function is not fully understood.
• Central mu opioid agonists can influence renal excretory function, but the precise mechanisms remain unclear.

Purpose of the Study:

• To investigate whether renal sympathetic nerves mediate the diuretic and antinatriuretic effects of central mu opioid agonist administration.
• To determine if central mu opioid receptor activation influences renal hemodynamics or sympathetic outflow.

Main Methods:

• Conscious Sprague-Dawley rats were administered dermorphin (a mu opioid agonist) intracerebroventricularly (i.c.v.) or intravenously (i.v.).
• Renal excretory function, glomerular filtration rate, and effective renal plasma flow were measured.
• Renal sympathetic nerve activity was monitored.
• Experiments were repeated in rats with chronic bilateral renal denervation.

Main Results:

• Intracerebroventricular dermorphin increased urine flow and decreased sodium excretion, an effect blocked by the mu opioid antagonist beta-funaltrexamine.
• Central dermorphin increased renal sympathetic nerve activity but did not alter renal hemodynamics.
• Renal denervation did not prevent the diuretic and antinatriuretic effects of i.c.v. dermorphin.

Conclusions:

• Central mu opioid agonists induce diuresis and antinatriuresis through mechanisms independent of renal sympathetic nerve activity.
• The antinatriuretic effect of central mu opioid agonists may involve direct effects on tubular sodium reabsorption via renal mu opioid receptors.