title: Sex differences in the renal vascular response to angiotensin II involves the Mas receptor.
abstract: OBJECTIVE
  The renin-angiotensin system (RAS) depressor arm, particularly renal angiotensin type 2 receptor (AT(2) R) and Mas receptor (masR) expression, is enhanced in females, which may contribute to renal and cardiovascular protection. We examined the hypotheses that masR activation increases renal blood flow (RBF) at rest and attenuates the reduction in RBF in response to angiotensin II (AngII) infusion in female rats. Furthermore, we postulated that combined activation of the AT(2) R and masR would produce a greater response than masR activation alone.
  
  
  METHODS
  In anaesthetized male and female Wistar rats, mean arterial pressure (MAP) and RBF responses during graded AngII infusion (30-1000 ng kg(-1)  min(-1)  i.v.) were assessed following pre-treatment with vehicle, the masR antagonist A779, or A779 plus the AT(2) R antagonist PD123319.
  
  
  RESULTS
  Basal MAP was not altered by any pre-treatment. Basal RBF decreased approx. 20% in female (P < 0.05), but not male rats in response to A779. However, basal RBF was not altered by A779 + PD123319. AngII infusion reduced RBF in a dose-related fashion (P(dose)  < 0.0001) and masR blockade did not alter the RBF response to AngII infusion in male or female rats. However, A779 + PD123319 attenuated the reduction in RBF response to AngII in females (P(group)  < 0.005), but not males.
  
  
  CONCLUSIONS
  The impact of the masR on renal haemodynamics appears to be sexually dimorphic, with greater effects in female than male rats. However, the paradoxical effects of dual AT(2) R and masR blockade suggest that a greater understanding of the complex interactions between RAS components is required before the therapeutic opportunities of AT(2) R and/or masR stimulation can be advanced.
authors: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: T
authors: T
authors: Safari
authors: M
authors: M
authors: Nematbakhsh
authors: L M
authors: LM
authors: Hilliard
authors: R G
authors: RG
authors: Evans
authors: K M
authors: KM
authors: Denton
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: C092006:7-Ala-angiotensin (1-7); D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; C073402:PD 123319