Intrarenal dopaminergic system regulates renin expression

Area of Science:

• Nephrology
• Endocrinology
• Molecular Biology

Background:

• Dopamine regulates salt reabsorption and renin release.
• In vitro studies suggest dopamine stimulates renin release via D1-like receptors.
• In vivo studies on dopamine's effect on renin release yield conflicting results.

Purpose of the Study:

• Investigate dopamine's in vivo regulation of renal renin release and synthesis.
• Clarify the role of macula densa cyclooxygenase-2 (COX-2) in dopamine's effect on renin.

Main Methods:

• Utilized D1-like receptor agonist (fenoldopam) and acetazolamide to inhibit proximal tubule salt reabsorption.
• Employed catechol-O-methyl transferase knockout (COMT(-/-)) mice to study effects of increased kidney dopamine.
• Administered low-salt and high-salt diets to assess renin and COX-2 expression.

Main Results:

• Fenoldopam and acetazolamide significantly inhibited renin release.
• COMT(-/-) mice showed blunted increases in renal COX-2 and renin expression/release on a low-salt diet.
• High-salt diet caused smaller decreases in renal renin expression in COMT(-/-) mice compared to wild-type.
• Fenoldopam stimulated renal renin expression in high salt-treated wild-type or COX-2 knockout mice.

Conclusions:

• Dopamine predominantly inhibits renal renin expression and release by suppressing macula densa COX-2.
• Dopamine can stimulate renal renin expression via D1-like receptors when renal cortical COX-2 activity is suppressed.