title: Treatment with the arginase inhibitor N(omega)-hydroxy-nor-L-arginine improves vascular function and lowers blood pressure in adult spontaneously hypertensive rat.
abstract: OBJECTIVE
  High vascular arginase activity and subsequent reduction in vascular nitric oxide production were recently reported in animal models of hypertension. The present study investigated the effects of in-vivo arginase inhibition on blood pressure and vascular function in adult spontaneously hypertensive rats.
  
  
  METHODS
  Ten-week-old spontaneously hypertensive rats and normotensive age-matched Wistar-Kyoto rats were treated with or without the selective arginase inhibitor N-hydroxy-nor-L-arginine for 3 weeks (10 or 40 mg/kg per day, intraperitoneally). Systolic blood pressure and cardiac rate were measured before and during treatment. Flow and pressure-dependent reactivity as well as remodeling of mesenteric arteries, acetylcholine-dependent vasodilation of aortic rings, cardiac hypertrophy, arginase activity and nitric oxide production were investigated in 13-week-old spontaneously hypertensive rats.
  
  
  RESULTS
  In spontaneously hypertensive rats, N-hydroxy-nor-L-arginine treatment decreased arginase activity (30-40%), reduced blood pressure ( approximately 35 mmHg) and improved the reactivity of mesenteric vessels. However, vascular and cardiac remodeling was not different between treated and untreated spontaneously hypertensive rats. In Wistar-Kyoto rats, N-hydroxy-nor-L-arginine did not affect blood pressure. Finally, arginase inhibition was associated with increased nitric oxide production. Consistent with this, the response of aortic rings to acetylcholine was fully restored by N-hydroxy-nor-L-arginine, and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester significantly reduced the effect of N-hydroxy-nor-L-arginine on flow-dependent vasodilation.
  
  
  CONCLUSIONS
  Pharmacological inhibition of arginase in adult spontaneously hypertensive rats decreases blood pressure and improves the reactivity of resistance vessels. These data represent in-vivo argument in favor of selective arginase inhibition as a new therapeutic strategy against hypertension.
authors.affiliation: Laboratory of Physiology, Pharmacology, Experimental Preventive Nutrition, EA 3921, 'Cellular and Metabolic Optimization', Faculty of Medicine and Pharmacy, Besancon University Hospital, Besancon, France.
authors.forename: Teddy
authors.initials: T
authors.lastname: Bagnost
authors.forename: Alain
authors.initials: A
authors.lastname: Berthelot
authors.forename: Malika
authors.initials: M
authors.lastname: Bouhaddi
authors.forename: Pascal
authors.initials: P
authors.lastname: Laurant
authors.forename: Claire
authors.initials: C
authors.lastname: André
authors.forename: Yves
authors.initials: Y
authors.lastname: Guillaume
authors.forename: Céline
authors.initials: C
authors.lastname: Demougeot
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014508:Urea / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007527:Isoenzymes; C404735:N(omega)-hydroxynorarginine; D009569:Nitric Oxide; D014508:Urea; D001120:Arginine; D001119:Arginase