title: Oxidative status in the macula densa modulates tubuloglomerular feedback responsiveness in angiotensin II-induced hypertension.
abstract: OBJECTIVE
  Tubuloglomerular feedback (TGF) is an important mechanism in control of signal nephron glomerular filtration rate. The oxidative stress in the macula densa, primarily determined by the interactions between nitric oxide (NO) and superoxide (O2-), is essential in maintaining the TGF responsiveness. However, few studies examining the interactions between and amount of NO and O2- generated by the macula densa during normal and hypertensive states.
  
  
  METHODS
  In this study, we used isolated perfused juxtaglomerular apparatus to directly measure the amount and also studied the interactions between NO and O2- in macula densa in both physiological and slow pressor Angiotensin II (Ang II)-induced hypertensive mice.
  
  
  RESULTS
  We found that slow pressor Ang II at a dose of 600 ng kg(-1) min(-1) for two weeks increased mean arterial pressure by 26.1 ± 5.7 mmHg. TGF response increased from 3.4 ± 0.2 μm in control to 5.2 ± 0.2 μm in hypertensive mice. We first measured O2- generation by the macula densa and found it was undetectable in control mice. However, O2- generation by the macula densa increased to 21.4 ± 2.5 unit min(-1) in Ang II-induced hypertensive mice. We then measured NO generation and found that NO generation by the macula densa was 138.5 ± 9.3 unit min(-1) in control mice. The NO was undetectable in the macula densa in hypertensive mice infused with Ang II.
  
  
  CONCLUSIONS
  Under physiological conditions, TGF response is mainly controlled by the NO generated in the macula densa; in Ang II induced hypertension, the TGF response is mainly controlled by the O2- generated by the macula densa.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: E Y
authors.initials: EY
authors.lastname: Lai
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Chandrashekar
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Shen
authors.forename: L A
authors.initials: LA
authors.lastname: Juncos
authors.forename: R
authors.initials: R
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide
keywords: hypertension; macula densa; oxidative stress; tubuloglomerular feedback
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