title: Renal medullary interstitial infusion is a flawed technique for examining vasodilator mechanisms in anesthetized rabbits.
abstract: BACKGROUND
  In rats, medullary interstitial (IMI) infusion is a useful technique for selective delivery of pharmacological agents to the renal medulla, in both acute and chronic experimental settings. We examined the feasibility of using this technique for delivery of vasodilators in rabbits, since this larger species would provide a number of advantages, particularly in long-term studies of circulatory control.
  
  
  METHODS
  Rabbits were anesthetized with pentobarbitone and artificially ventilated. Catheters were placed in a side branch of the renal artery and/or the renal medullary interstitium. Renal blood flow (RBF) was determined by transit-time ultrasound flowmetry, and blood flow in the cortex and medulla was estimated by laser Doppler flowmetry.
  
  
  RESULTS
  Pilot studies showed that renal arterial (IRA) infusions of bradykinin (10-300 ng/kg/min) and adenosine (1-10 ng/kg/min) produced only transient renal vasodilatation. IRA infusions of methylamine hexamethylene methylamine (MAHMA) NONOate (100-1000 ng/kg/min) and acetylcholine (10-250 ng/kg/min) produced dose-dependent and sustained increases in RBF and reductions in arterial pressure at the highest doses. However, IMI infusion of the same doses did not consistently increase medullary laser Doppler flux (MLDF). After IRA MAHMA NONOate and IMI acetylcholine, RBF fell to below its resting level. IRA boluses of acetylcholine (10-1250 ng/kg), bradykinin (2-250 ng/kg), and MAHMA NONOate (100-3000 ng/kg) dose-dependently increased RBF and CLDF and MLDF.
  
  
  CONCLUSIONS
  We had previously validated the IMI infusion technique for intramedullary delivery of vasoconstrictors in rabbits. Our present results indicate that this technique has limited application for delivery of vasodilator agents, in part because counterregulatory vasoconstrictor mechanisms are activated.
authors.affiliation: Department of Physiology, Monash University, P.O. Box 13F, Victoria 3800, Australia.
authors.forename: Aparna
authors.initials: A
authors.lastname: Kalyan
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Eppel
authors.forename: Warwick P
authors.initials: WP
authors.lastname: Anderson
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Oliver
authors.forename: Roger G
authors.initials: RG
authors.lastname: Evans
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D006834:Hydrazines / Q000494:pharmacology; D007262:Infusions, Intravenous / Q000379:methods*; D007679:Kidney Medulla / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C105785:1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl; D006834:Hydrazines; D014665:Vasodilator Agents; D000241:Adenosine; D000109:Acetylcholine; D001920:Bradykinin