title: The vasodilatory effect of testosterone on renal afferent arterioles.
abstract: BACKGROUND
  Sex differences exist in a variety of cardiovascular and renal diseases, and testosterone may contribute to the discrepancy. Afferent arterioles (Af-Arts) are the major resistance vessels in the kidney, and they play an important role in the development of renal injury and hypertension.
  
  
  OBJECTIVE
  We sought to determine the acute effect and underlying mechanism(s) of action of testosterone on Af-Arts.
  
  
  METHODS
  The mRNA expression of androgen receptors (ARs) in microdissected Af-Arts was measured by reverse transcription-polymerase chain reaction (RT-PCR). An in vitro microperfusion model was used to measure the diameter of Af-Arts in mice. Nitric oxide (NO) was evaluated by an NO-sensitive fluorescent dye, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate.
  
  
  RESULTS
  Testosterone had no effect on microperfused Af-Arts when added to the bath. Therefore, we preconstricted the Af-Arts to approximately 30% with norepinephrine (10(-6) M); administration of testosterone (10(-9)-10(-7) M) subsequently dilated the Af-Arts in a dose-dependent manner (P < 0.001; n = 7). The AR mRNA was expressed in microdissected Af-Arts measured by RT-PCR. An AR antagonist, flutamide (10(-5) M), totally blocked the testosterone (10(-8) M)-induced vasodilator effect. Mean (SEM) NO production of the Af-Art wall was increased when testosterone was added to the bath solution after norepinephrine treatment, from 278.4 (12.1) U/min to 351.2 (33.1) U/min (P < 0.05; n = 3). In the presence of NO inhibition with N(G)-nitro-L-arginine methyl ester (3 × 10(-4) M), the testosterone-induced dilatation was blunted compared with norepinephrine (P < 0.05).
  
  
  CONCLUSIONS
  Testosterone dilated preconstricted mouse Af-Arts in a dose-dependent manner by activation of ARs and partially mediated by NO.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Yiling
authors.initials: Y
authors.lastname: Fu
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
authors.forename: Luis A
authors.initials: LA
authors.lastname: Juncos
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D011944:Receptors, Androgen; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013739:Testosterone