Complex reinnervation pattern after unilateral renal denervation in rats.

Area of Science:

• Nephrology
• Cardiovascular Science
• Neuroscience

Background:

• Resistant arterial hypertension is a condition treated with renal denervation (DNX).
• Sympathetic efferent nerves regrow after DNX, but afferent nerve reinnervation is less understood.
• Recent studies suggest afferent nerve reinnervation in the renal pelvis after unilateral DNX.

Purpose of the Study:

• To investigate intrarenal perivascular afferent and sympathetic efferent nerve changes after unilateral surgical DNX.
• To compare nerve regeneration and neurotransmitter recovery in denervated versus non-denervated kidneys over time.

Main Methods:

• Used Sprague-Dawley rats for unilateral DNX.
• Examined kidney sections using markers for afferents (CGRP), efferents (TH), and vasculature (smooth muscle actin).
• Quantified CGRP and norepinephrine (NE) levels using ELISA and mass spectrometry at 1, 4, and 12 weeks post-DNX.

Main Results:

• DNX significantly reduced TH and CGRP by 90-95% within 1 week.
• After 12 weeks, TH and CGRP returned to baseline levels, with a shift towards afferent innervation.
• CGRP content fully recovered by 12 weeks post-DNX, but norepinephrine (NE) levels did not fully recover.

Conclusions:

• Morphological reinnervation and neurotransmitter recovery of afferent nerves occur within 12 weeks after DNX.
• Despite sympathetic nerve regrowth, NE levels remain suboptimal.
• A potential long-term net surplus of afferent nerve influence may contribute to the blood pressure-lowering effects of DNX.