Chemical Renal Denervation in the Rat

Journal Article · Tue Dec 03 00:00:00 EST 2013 · Cardiovascular and Interventional Radiology

DOI:https://doi.org/10.1007/S00270-013-0796-7· OSTI ID:22318101

Davalian, Dariush ^[1]; Donn, Rosy; Hu, Jie ^[2]; Rieser, Matthew; Stolarik, DeAnne ^[3]

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1. Abbott Vascular, Innovation Incubator (United States)
2. Abbott Vascular, Bioanalytical and Material Characterization (United States)
3. Abbvie, Analytical Pharmacology (United States)

Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

• OSTI ID: 22318101
• Journal Information: Cardiovascular and Interventional Radiology, Vol. 37, Issue 1; Other Information: Copyright (c) 2014 Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE); http://www.springer-ny.com; Country of input: International Atomic Energy Agency (IAEA); ISSN 0174-1551
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ALCOHOLS
ARTERIES
AUGMENTATION
BLOOD PRESSURE
CARBONIC ACID DERIVATIVES
DELIVERY
DOSE-RESPONSE RELATIONSHIPS
DOSES
HETEROCYCLIC COMPOUNDS
KIDNEYS
LIQUID COLUMN CHROMATOGRAPHY
MASS SPECTROSCOPY
NORADRENALINE
ORGANIC NITROGEN COMPOUNDS
PATIENTS
PHENOL
RATS
SALICYLIC ACID
SPACE
STRIPPING
SURGERY