title: The effect of losartan on differential reflex control of sympathetic nerve activity in chronic kidney disease.
abstract: BACKGROUND
  The effect of angiotensin II type I receptor (AT1R) inhibition on the pattern of reflex sympathetic nerve activity (SNA) to multiple target organs in the Lewis polycystic kidney (LPK) rat model of chronic kidney disease was determined.
  
  
  METHODS
  Mean arterial pressure (MAP), splanchnic SNA (sSNA), renal SNA (rSNA) and lumbar SNA (lSNA) were recorded in urethane-anaesthetized LPK and Lewis controls (total n = 39). Baroreflex, peripheral and central chemoreflex, and somatosensory reflex control of SNA (evoked by phenylephrine/sodium nitroprusside infusion, 10% O2 in N2 or 100% N2 ventilation, 5% CO2 ventilation and sciatic nerve stimulation, respectively) were determined before and after administration of losartan (AT1R antagonist 3 mg/kg, intravenous).
  
  
  RESULTS
  Baseline MAP was higher in LPK rats and baroreflex control of sSNA and rSNA, but not lSNA, was reduced. Losartan reduced MAP in both strains and selectively improved baroreflex gain for sSNA (-1.2 ± 0.1 vs. -0.7 ± 0.07 %/mmHg; P < 0.05) in LPK. The peripheral and central chemoreflex increased MAP and all SNA in Lewis controls, but reduced or had no effect on these parameters, respectively, in LPK. The SNA response to somatosensory stimulation was biphasic, with latency to second peak less in LPK. Losartan ameliorated the depressor and sympathoinhibitory responses to peripheral chemoreflex stimulation in the LPK, but did not alter the central chemoreflex or somatosympathetic responses.
  
  
  CONCLUSIONS
  Inhibition of the AT1R selectively improved baroreflex control of sSNA and peripheral chemoreflex control of all three sympathetic nerve outflows in the LPK rat, suggesting these anomalies in reflex function are driven in part by angiotensin II.
authors.affiliation: aAustralian School of Advanced Medicine, Macquarie University bHeart Research Institute and University of Sydney, Newtown, Sydney, New South Wales, Australia.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Yao
authors.forename: Cara M
authors.initials: CM
authors.lastname: Hildreth
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Farnham
authors.forename: Manash
authors.initials: M
authors.lastname: Saha
authors.forename: Qi-Jian
authors.initials: QJ
authors.lastname: Sun
authors.forename: Paul M
authors.initials: PM
authors.lastname: Pilowsky
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Phillips
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017776:Autonomic Pathways / Q000187:drug effects; D017704:Baroreflex / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008161:Lumbosacral Region / Q000294:innervation; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D009599:Nitroprusside; D010656:Phenylephrine; D019808:Losartan