title: Changes in renal blood flow in response to sympathomimetics in the rat transplanted and denervated kidney.
abstract: BACKGROUND
  Renal denervation and re-innervation may affect vascular responses to sympathomimetics, which may play a role in the maintainance of renal blood flow (RBF) following renal transplantation. The purpose of the present study was to elucidate pharmacological alteration of the renal sympathetic response following kidney transplantation. Using the rat kidney transplantation model, we focused on responses to various sympathomimetics in order to investigate the effects of sympathetic denervation and functional remodulation mechanisms in the transplanted kidney.
  
  
  METHODS
  Male isogenic rats underwent unilateral kidney denervation or kidney transplantation accompanied by unilateral native nephrectomy. Renal blood flow was evaluated using a laser Doppler flow meter following bolus injection of 50 microg/kg dopamine and continuous infusion of 60 microg/min phenylephrine (PE) at 0, 30, 60, 90 and 240 days after transplantation as well as at 30 days after denervation.
  
  
  RESULTS
  Bolus injection of dopamine (50 microg/kg) induced an initial reduction in RBF (that of alpha-adrenoceptors) followed by a long-lasting increase in RBF (that of beta-adrenoceptors) in the native kidney. In grafted or denervated kidneys, the dopamine-induced decrease in RBF mediated by alpha-adrenoceptors was markedly enhanced while the increase in RBF mediated by an action of dopamine on beta-adrenoceptors was blunted. The effects of the post-transplant period on vascular responses to dopamine were significant, but not completely synchronized with the native kidney, even at 240 days. Continuous infusion of PE (60 microg/min) produced a gradual increase in RBF in the native kidney, whereas a sudden reduction (i.e. breakthrough in autoregulation) was observed in the denervated and transplanted kidney.
  
  
  CONCLUSIONS
  The responses to sympathomimetics in the grafted kidney were shifted towards flow reduction (i.e. enhanced vasoconstriction via stimulation of alpha-adrenoceptors and blunted vasodilatation via stimulation of beta-adrenoceptors. This functional impairment was recovered in a time-dependent manner. In addition, the hemodynamic autoregulation system in the kidney deteriorated following transplantation or denervation.
authors.affiliation: Department of Urology, Hokkaido University School of Medicine, Sapporo, Japan. moritak@athene.hh.ri.ccf.org
authors.forename: K
authors.initials: K
authors.lastname: Morita
authors.forename: T
authors.initials: T
authors.lastname: Seki
authors.forename: K
authors.initials: K
authors.lastname: Nonomura
authors.forename: T
authors.initials: T
authors.lastname: Koyanagi
authors.forename: M
authors.initials: M
authors.lastname: Yoshioka
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000818:Animals; D017763:Autonomic Denervation; D001341:Autonomic Nervous System / Q000187:drug effects / Q000601:surgery; D002316:Cardiotonic Agents / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005500:Follow-Up Studies; D007668:Kidney / Q000098:blood supply* / Q000294:innervation; D016030:Kidney Transplantation / Q000502:physiology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D013566:Sympathomimetics / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D013566:Sympathomimetics; D010656:Phenylephrine; D004298:Dopamine