Chemical renal denervation in the rat

Area of Science:

• Pharmacology
• Nephrology
• Surgical Innovation

Background:

• Renal denervation shows promise for treating drug-resistant hypertension.
• Novel approaches, including local drug delivery, are being explored to enhance denervation efficacy.

Purpose of the Study:

• To develop and validate a rat model for assessing renal denervation efficacy.
• To evaluate chemical delivery to the renal artery's periadventitial space using norepinephrine depletion as a biomarker.

Main Methods:

• Renal denervation was performed on 90 rats.
• Efficacy was assessed by measuring renal norepinephrine (NE) content via liquid chromatography-mass spectrometry.
• Various agents (phenol, hypertonic saline, guanethidine, salicylic acid, paclitaxel) were tested for periadventitial delivery.

Main Results:

• Surgical denervation and periadventitial chemical delivery effectively depleted renal NE.
• Hypertonic saline, salicylic acid, guanethidine, and paclitaxel all demonstrated denervation efficacy.
• A dose-dependent response was observed with paclitaxel application.

Conclusions:

• A validated rat model for evaluating perivascular renal artery drug delivery was established.
• The model successfully demonstrated the denervation efficacy of several neurotoxic agents and paclitaxel.
• This model can be used to assess novel renal denervation strategies.