title: Activation of cardiac renin-angiotensin system and plasminogen activator inhibitor-1 gene expressions in oral contraceptive-induced cardiometabolic disorder.
abstract: BACKGROUND
  Clinical studies have shown that combined oral contraceptive (COC) use is associated with cardiometabolic disturbances. Elevated renin-angiotensin system (RAS) and plasminogen activator inhibitor-1 (PAI-1) have also been implicated in the development of cardiometabolic events.
  
  
  OBJECTIVE
  To determine the effect of COC treatment on cardiac RAS and PAI-1 gene expressions, and whether the effect is circulating aldosterone or corticosterone dependent.
  
  
  METHODS
  Female rats were treated (p.o.) with olive oil (vehicle) or COC (1.0 µg ethinylestradiol and 10.0 µg norgestrel) daily for six weeks.
  
  
  RESULTS
  COC treatment led to increases in blood pressure, HOMA-IR, Ace1 mRNA, Atr1 mRNA, Pai1 mRNA, cardiac PAI-1, plasma PAI-1, C-reactive protein, uric acid, insulin and corticosterone. COC treatment also led to dyslipidemia, decreased glucose tolerance and plasma 17β-estradiol.
  
  
  CONCLUSIONS
  These results demonstrates that hypertension and insulin resistance induced by COC is associated with increased cardiac RAS and PAI-1 gene expression, which is likely to be through corticosterone-dependent but not aldosterone-dependent mechanism.
authors.affiliation: a Department of Physiology , Cardiovascular and Molecular Physiology Unit, College of Health Sciences University of Ilorin , P.M.B. 1515 , Ilorin , Nigeria.|b Cardiovascular Research Institute, Kyungpook National University School of Medicine , Daegu , Republic of Korea.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Olatunji
authors.affiliation: a Department of Physiology , Cardiovascular and Molecular Physiology Unit, College of Health Sciences University of Ilorin , P.M.B. 1515 , Ilorin , Nigeria.
authors.forename: Taofeek O
authors.initials: TO
authors.lastname: Usman
authors.affiliation: b Cardiovascular Research Institute, Kyungpook National University School of Medicine , Daegu , Republic of Korea.|c Korea Promotion Institute for Traditional Medicine Industry , Gyeongsan , Gyeongbuk , Republic of Korea , and.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Seok
authors.affiliation: b Cardiovascular Research Institute, Kyungpook National University School of Medicine , Daegu , Republic of Korea.|d Department of Pharmacology , Kyungpook National University School of Medicine , Daegu , Republic of Korea.
authors.forename: In-Kyeom
authors.initials: IK
authors.lastname: Kim
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D050171:Dyslipidemias / Q000209:etiology; D019304:Ethinyl Estradiol-Norgestrel Combination / Q000009:adverse effects*; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology; D006321:Heart / Q000187:drug effects*; D006946:Hyperinsulinism / Q000209:etiology; D006973:Hypertension / Q000209:etiology; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000819:agonists* / Q000097:blood / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D003277:Contraceptives, Oral, Combined; D017395:Plasminogen Activator Inhibitor 1; C547314:Serpine1 protein, rat; D000450:Aldosterone; D019304:Ethinyl Estradiol-Norgestrel Combination; D064007:Ataxia Telangiectasia Mutated Proteins; D007703:Peptidyl-Dipeptidase A; D003345:Corticosterone
keywords: Angiotensin-converting enzyme; angiotensin II receptor; cardiac gene expression; oral contraceptive; plasminogen activator inhibitor-1