title: Arginase inhibition alleviates hypertension in the metabolic syndrome.
abstract: OBJECTIVE
  We have previously shown that arginase inhibition alleviates hypertension associated with in a diabetic animal model. Here, we investigated the protective effect of arginase inhibition on hypertension in metabolic syndrome.
  
  
  METHODS
  Metabolic syndrome was induced in rats by administration of fructose (10% in drinking water) for 12 weeks to induce vascular dysfunction. Three arginase inhibitors (citrulline, norvaline and ornithine) were administered daily in the last 6 weeks of study before and tail BP was recorded in conscious animals. Concentration response curves for phenylephrine (PE), KCl and ACh in addition to ACh-induced NO generation were obtained in thoracic aorta rings. Serum glucose, insulin, uric acid and lipid profile were determined as well as reactive oxygen species (ROS) and arginase activity.
  
  
  RESULTS
  Arginase activity was elevated in metabolic syndrome while significantly inhibited by citrulline, norvaline or ornithine treatment. Metabolic syndrome was associated with elevations in systolic and diastolic BP, while arginase inhibition significantly reduced elevations in diastolic and systolic BP. Metabolic syndrome increased vasoconstriction responses of aorta to PE and KCl and decreased vasorelaxation to ACh, while arginase inhibition completely prevented impaired responses to ACh. In addition, arginase inhibition prevented impaired NO generation and exaggerated ROS formation in metabolic syndrome. Furthermore, arginase inhibition significantly reduced hyperinsulinaemia and hypertriglyceridaemia without affecting hyperuricaemia or hypercholesterolaemia associated with metabolic syndrome.
  
  
  CONCLUSIONS
  Arginase inhibition alleviates hypertension in metabolic syndrome directly through endothelial-dependent relaxation/NO signalling protection and indirectly through inhibition of insulin resistance and hypertriglyceridaemia.
authors: Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. helbassossy@kau.edu.eg
authors: Hany M
authors: HM
authors: El-Bassossy
authors: Rania
authors: R
authors: El-Fawal
authors: Ahmed
authors: A
authors: Fahmy
authors: Malcolm L
authors: ML
authors: Watson
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002956:Citrulline / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006946:Hyperinsulinism / Q000209:etiology / Q000517:prevention & control; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control*; D015228:Hypertriglyceridemia / Q000209:etiology / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000819:agonists / Q000378:metabolism; D009952:Ornithine / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D000960:Hypolipidemic Agents; D017382:Reactive Oxygen Species; D002956:Citrulline; D009569:Nitric Oxide; C005313:norvaline; D009952:Ornithine; D001119:Arginase; D014633:Valine