title: Sex differences in renal responses to hyperglycemia, L-arginine, and L-NMMA in humans with uncomplicated type 1 diabetes.
abstract: OBJECTIVE
  Women exhibit exaggerated renal hemodynamic responses to hyperglycemia, which may promote kidney disease progression. Our aim was to determine if increased nitric oxide generation by l-arginine infusion would reverse this deleterious response to clamped hyperglycemia in women with type 1 diabetes mellitus.
  
  
  METHODS
  Renal function, blood pressure, and plasma cyclic guanosine monophosphate (cGMP) were measured in 20 men and 15 women with type 1 diabetes mellitus during clamped euglycemia and clamped hyperglycemia. Renal function, blood pressure, and plasma cGMP responses to graded infusions of intravenous l-arginine and N(G)-monomethyl-l-arginine (l-NMMA) were measured during clamped hyperglycemia.
  
  
  RESULTS
  Subjects were young, normotensive, normoalbuminuric men and women who adhered to a high-sodium, moderate-protein diet. Plasma cGMP levels during euglycemia were generally lower in men compared with women, and systolic blood pressure (SBP) was higher in men. In response to hyperglycemia, cGMP levels did not change in men but did decline in women (Δ-1.10 ± 0.20 vs. Δ+0.05 ± 0.20 pmol/L, between-group effect of hyperglycemia on cGMP; P = 0.012). Hyperglycemia also was associated with an increase in SBP, glomerular filtration rate (GFR) (124 ± 6 to 143 ± 7 mL/min/1.73 m(2); P = 0.003) and filtration fraction (FF) in women, but these parameters did not change in men. In response to l-arginine during hyperglycemia, the increase in cGMP was exaggerated in women versus men and GFR and FF decreased in women only, back toward baseline values observed during clamped euglycemia. l-NMMA infusion did not exaggerate changes in hemodynamic function in response to hyperglycemia.
  
  
  CONCLUSIONS
  l-Arginine reversed the renal hemodynamic effects of hyperglycemia in women, suggesting that nitric oxide is an important regulator of sex-dependent vascular responses to hyperglycemia in humans.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada. david.cherney@uhn.on.ca
authors.forename: David Z I
authors.initials: DZ
authors.lastname: Cherney
authors.forename: James W
authors.initials: JW
authors.lastname: Scholey
authors.forename: Etienne B
authors.initials: EB
authors.lastname: Sochett
mesh_terms: D000328:Adult; D001120:Arginine / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D012727:Sex Characteristics; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000627:therapeutic use*
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine