title: AT1 receptors mediate angiotensin II-induced release of nitric oxide in afferent arterioles.
abstract: BACKGROUND
  Recent studies have indicated that angiotensin II (Ang II) possibly activates the nitric oxide (NO) system. We investigated the role of AT receptor subtypes (AT-R) in mediating the Ang II-induced NO release in afferent arterioles (Af) of mice.
  
  
  METHODS
  Isolated Af of mice were perfused, and the isotonic contraction measured. Further, NO release was determined using DAF-FM, a fluorescence indicator for NO. Moreover, we qualitatively assessed the expression of AT-R at the mRNA level using reverse transcription-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Ang II reduced luminal diameters dose dependently (67.3 +/- 6.3% at 10(-6) mol/L). Inhibition of AT2-R with PD123.319 did not change the Ang II contractile response. AT1-R blockade with ZD7155 inhibited contraction. Stimulation of AT2-R during AT1-R inhibition with ZD7155, and preconstriction with norepinephrine (NE) had no influence on the diameter. Drug application via the perfusion pipette changed flow and pressure, and enhanced NO fluorescence by DeltaF = 4.0 +/- 0.4% (N= 14, background). Luminal application of Ang II (10(-7) mol/L) increased the NO fluorescence by DeltaF = 9.9 +/- 1.2% (N= 8). AT1-R blockade blunted the increase to background levels (DeltaF to 4.0 +/- 0.3%, N= 6, P < 0.05), but AT2-R blockade did not (8.1 +/- 0.9%, N= 9). L-NAME nearly abolished the Ang II effect on the NO fluorescence (DeltaF = 1.6 +/- 0.5% (N= 8). NE did not increase NO release beyond the background levels. RT-PCR showed expression of both AT1-R and AT2-R.
  
  
  CONCLUSIONS
  The results indicate an Ang II-induced NO release in Af of mice, which is mediated by AT1-R. Thus, Ang II balances its own constrictor action in Af. This control mechanism is very important in view of high renin and angiotensin II concentration in the juxtaglomerular apparatus.
authors.affiliation: Institute of Physiology, Humboldt-University of Berlin, University Hospital Charité, Berlin, Germany. andreas.patzak@charite.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Patzak
authors.forename: En Y
authors.initials: EY
authors.lastname: Lai
authors.forename: Ralf
authors.initials: R
authors.lastname: Mrowka
authors.forename: Andreas
authors.initials: A
authors.lastname: Steege
authors.forename: Pontus B
authors.initials: PB
authors.lastname: Persson
authors.forename: A Erik G
authors.initials: AE
authors.lastname: Persson
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D011945:Receptors, Angiotensin / Q000235:genetics; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide