title: Chemical renal denervation in the rat.
abstract: BACKGROUND
  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(-5) M through 10(-2) M paclitaxel.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Innovation Incubator, Abbott Vascular, 3200 Lakeside Drive, Santa Clara, CA, 95054, USA, paul.consigny@av.abbott.com.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Consigny
authors.forename: Dariush
authors.initials: D
authors.lastname: Davalian
authors.forename: Rosy
authors.initials: R
authors.lastname: Donn
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Matthew
authors.initials: M
authors.lastname: Rieser
authors.forename: Deanne
authors.initials: D
authors.lastname: Stolarik
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D003714:Denervation / Q000379:methods*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006145:Guanethidine / Q000494:pharmacology; D006973:Hypertension / Q000628:therapy; D007668:Kidney / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D013058:Mass Spectrometry; D009638:Norepinephrine / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D019800:Phenol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000494:pharmacology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology
chemical_list: D012462:Saline Solution, Hypertonic; D019800:Phenol; D020156:Salicylic Acid; D017239:Paclitaxel; D009638:Norepinephrine; D006145:Guanethidine