title: Therapeutic interventions using a combination of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction in rats: modulation through ATP-sensitive K+ channels and eNOS.
abstract: BACKGROUND
  Effective diet/drug combinations may show additive or synergistic effects in reducing endothelial risk factors vis-à-vis monotherapies. The study evaluated the effect of combined therapy of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats.
  
  
  METHODS
  Forty-eight male Wistar rats (180-220 g) were randomized into eight groups; control, sodium arsenite (1.5 mg/kg/day) exposed, sodium arsenite exposure followed by treatment with Telmisartan, omega 3-fatty acids, the combination and/or endothelial modulators for 2 weeks depending on the allocated group. VED was assessed by estimating vascular reactivity. Serum thiobarbituric acid-reactive substances (TBARS), nitrite/nitrate levels, reduced glutathione (GSH) levels, superoxide dismutase (SOD) activity, serum cholesterol and triglyceride levels were also determined.
  
  
  RESULTS
  Sodium arsenite produced VED by attenuating acetylcholine-induced endothelial relaxation (% Rmax= 45.36), decreasing levels of serum nitrite/nitrate (9.28 μM/mg protein), GSH (16.06 μg/mg of protein), SOD activity (30.69 units/mg protein) and increasing TBARS (0.19 µM/mg protein) compared with control group. The combined therapy with Telmisartan (10 mg/kg/day) and omega 3-fatty acids (180 mg/kg/day) (% Rmax = 80.93, 13.09 µM/mg protein, 25.93 μg/mg of protein, 57.84 units/mg protein and 0.08 µM/mg protein, respectively) significantly abolished the respective derangements induced by sodium arsenite. Further, this combination significantly prevented rise in serum cholesterol and triglyceride levels that was induced by sodium arsenite. However, the ameliorative effects of this combination were abated by N-omega-nitro-L-arginine methyl ester (L-NAME) and glibenclamide.
  
  
  CONCLUSIONS
  Combined therapy of Telmisartan and omega 3-fatty acids attenuated VED, by activating enzyme nitric oxide synthase (eNOS) through opening of ATP-sensitive K(+) channels.
authors: Abhijit
authors: A
authors: Nirwane
authors: Vivek
authors: V
authors: Pawar
authors: Anuradha
authors: A
authors: Majumdar
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic; D018053:Arsenites; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D017670:Sodium Compounds; D000077333:Telmisartan; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides / Q000097:blood; D014652:Vascular Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D018053:Arsenites; D001562:Benzimidazoles; D001565:Benzoates; D002317:Cardiovascular Agents; D015525:Fatty Acids, Omega-3; D054086:KATP Channels; D017670:Sodium Compounds; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; C017947:sodium arsenite; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D005905:Glyburide; D000077333:Telmisartan; D019331:NG-Nitroarginine Methyl Ester