title: Effects of Arginase Inhibition in Hypertensive Hyperthyroid Rats.
abstract: BACKGROUND
  This study analyzed the effects of chronic administration of N[omega]-hydroxy-nor-l-arginine (nor-NOHA), an inhibitor of arginase, on the hemodynamic, oxidative stress, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats.
  
  
  METHODS
  Four groups of male Wistar rats were used: control, nor-NOHA-treated (10 mg/kg/day), thyroxine (T4)-treated (75 μg/rat/day), and thyroxine- plus nor-NOHA-treated rats. All treatments were maintained for 4 weeks. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, morphologic, metabolic, plasma, and renal variables were measured. Arginase I and II protein abundance and arginase activity were measured in aorta, heart, and kidney.
  
  
  RESULTS
  The T4 group showed increased arginase I and II protein abundance, arginase activity, SBP, HR, plasma nitrates/nitrites (NOx), brainstem and urinary isoprostanes, proteinuria and cardiac and renal hypertrophy in comparison to control rats. In hyperthyroid rats, chronic nor-NOHA prevented the increase in SBP and HR and decreased proteinuria in association with an increase in plasma NOx and a decrease in brainstem and urinary isoprostanes. In normal rats, nor-NOHA treatment did not significantly change any hemodynamic, morphologic, or renal variables. Acute nor-NOHA administration did not affect renal or systemic hemodynamic variables in normal or T4-treated rats.
  
  
  CONCLUSIONS
  Hyperthyroidism in rats is associated with the increased expression and activity of arginase in aorta, heart, and kidney. Chronic arginase inhibition with nor-NOHA suppresses the characteristic hemodynamic manifestations of hyperthyroidism in association with a reduced oxidative stress. These results indicate an important role for arginase pathway alterations in the cardiovascular and renal abnormalities of hyperthyroidism.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada. Universidad de Granada, Granada, Spain;
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez-Gómez
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada. Universidad de Granada, Granada, Spain; Departamento de Fisiología, Facultad de Medicina, Murcia, Spain;
authors.forename: Juan
authors.initials: J
authors.lastname: Manuel Moreno
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada. Universidad de Granada, Granada, Spain; Departamento de Farmacología, Facultad de Farmacia, Granada, Spain;
authors.forename: Rosario
authors.initials: R
authors.lastname: Jimenez
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada. Universidad de Granada, Granada, Spain; Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Quesada
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada. Universidad de Granada, Granada, Spain; Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Montoro-Molina
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada. Universidad de Granada, Granada, Spain;
authors.forename: Pablo
authors.initials: P
authors.lastname: Vargas-Tendero
authors.affiliation: Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada. Universidad de Granada, Granada, Spain; Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Wangensteen
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada. Universidad de Granada, Granada, Spain; fvargas@ugr.es.
authors.forename: Félix
authors.initials: F
authors.lastname: Vargas
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure; D001933:Brain Stem / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006339:Heart Rate; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006980:Hyperthyroidism / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D028421:Isoprostanes / Q000652:urine; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D011897:Random Allocation; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D028421:Isoprostanes; C404735:N(omega)-hydroxynorarginine; D013963:Thyroid Hormones; D009569:Nitric Oxide; D001120:Arginine; D001119:Arginase
keywords: arginase activity; blood pressure; hypertension; hyperthyroidism; nor-NOHA; oxidative stress.