title: Sinapic acid prevents hypertension and cardiovascular remodeling in pharmacological model of nitric oxide inhibited rats.
abstract: OBJECTIVE
  Hypertensive heart disease is a constellation of abnormalities that includes cardiac fibrosis in response to elevated blood pressure, systolic and diastolic dysfunction. The present study was undertaken to examine the effect of sinapic acid on high blood pressure and cardiovascular remodeling.
  
  
  METHODS
  An experimental hypertensive animal model was induced by L-NAME intake on rats. Sinapic acid (SA) was orally administered at a dose of 10, 20 and 40 mg/kg body weight (b.w.). Blood pressure was measured by tail cuff plethysmography system. Cardiac and vascular function was evaluated by Langendorff isolated heart system and organ bath studies, respectively. Fibrotic remodeling of heart and aorta was assessed by histopathologic analyses. Oxidative stress was measured by biochemical assays. mRNA and protein expressions were assessed by RT-qPCR and western blot, respectively. In order to confirm the protective role of SA on endothelial cells through its antioxidant property, we have utilized the in vitro model of H2O2-induced oxidative stress in EA.hy926 endothelial cells.
  
  
  RESULTS
  Rats with hypertension showed elevated blood pressure, declined myocardial performance associated with myocardial hypertrophy and fibrosis, diminished vascular response, nitric oxide (NO) metabolites level, elevated markers of oxidative stress (TBARS, LOOH), ACE activity, depleted antioxidant system (SOD, CAT, GPx, reduced GSH), aberrant expression of TGF-β, β-MHC, eNOS mRNAs and eNOS protein. Remarkably, SA attenuated high blood pressure, myocardial, vascular dysfunction, cardiac fibrosis, oxidative stress and ACE activity. Level of NO metabolites, antioxidant system, and altered gene expression were also repaired by SA treatment. Results of in vitro study showed that, SA protects endothelial cells from oxidative stress and enhance the production of NO in a concentration dependent manner.
  
  
  CONCLUSIONS
  Taken together, these results suggest that SA may have beneficial role in the treatment of hypertensive heart disease by attenuating fibrosis and oxidative stress through its antioxidant potential.
authors.affiliation: Cardiovascular Biology Lab, Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India.
authors.forename: Thangarasu
authors.initials: T
authors.lastname: Silambarasan
authors.affiliation: Cardiovascular Biology Lab, Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India; Vascular Biology Lab, AU-KBC Research Centre, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Jeganathan
authors.initials: J
authors.lastname: Manivannan
authors.affiliation: Vascular Biology Lab, AU-KBC Research Centre, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Mani
authors.initials: M
authors.lastname: Krishna Priya
authors.affiliation: Vascular Biology Lab, AU-KBC Research Centre, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Suganya
authors.affiliation: Vascular Biology Lab, AU-KBC Research Centre, Anna University, Chennai, Tamil Nadu, India; Department of Biotechnology, Anna University, Chennai, Tamil Nadu, India.
authors.forename: Suvro
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Cardiovascular Biology Lab, Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India.
authors.forename: Boobalan
authors.initials: B
authors.lastname: Raja
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000633:toxicity; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D000975:Antioxidants; D003373:Coumaric Acids; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; C073734:sinapinic acid; D019331:NG-Nitroarginine Methyl Ester