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Title: Chemical Renal Denervation in the Rat

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 ratmore » 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.« less
Authors:
;  [1] ; ;  [2] ; ;  [3]
  1. Abbott Vascular, Innovation Incubator (United States)
  2. Abbott Vascular, Bioanalytical and Material Characterization (United States)
  3. Abbvie, Analytical Pharmacology (United States)
Publication Date:
OSTI Identifier:
22318101
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cardiovascular and Interventional Radiology; Journal Volume: 37; Journal 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)
Country of Publication:
United States
Language:
English
Subject:
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