title: Reduced expression of endothelial connexins 43 and 37 in hypertensive rats is rectified after 7-day carvedilol treatment.
abstract: BACKGROUND
  The aim of this study was to clarify the response of endothelial connexins to hypertension and antihypertensive drugs.
  
  
  METHODS
  Rats remained normotensive (group 1, N = 10) or were made hypertensive using N(omega)-nitro-L-arginine methyl ester (L-NAME) (groups 2 to 4, N = 10/group). Seven weeks later groups 3 and 4 were respectively fed atenolol or carvedilol daily for 7 days and the aortic endothelial gap junctions were analyzed. In parallel the effects of atenolol, carvedilol, labetalol, vitamin C, and vitamin E on connexin43 (Cx43) in human umbilical vein endothelial cells (HUVEC) were compared.
  
  
  RESULTS
  Endothelial Cx43 was reduced by 35% and Cx37 by 59% in hypertensive rats (P < .001). The reduction was recovered fully by carvedilol but only partially by atenolol (P < .05), although both drugs lowered the blood pressure to similar levels. Cx40 remained stationary in all groups. In HUVEC, carvedilol (10 microg/mL) increased Cx43 protein expression by >70% (P < .01), whereas other drugs had minimal effects. The upregulation by carvedilol was associated with increased transcripts and decreased proteolysis of Cx43.
  
  
  CONCLUSIONS
  The study showed that L-NAME-induced hypertension has differential effects on endothelial connexins, which respond variously to carvedilol and atenolol. In HUVEC carvedilol directly upregulates endothelial Cx43 and the effect is independent of its antioxidant activity.
authors.affiliation: Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hung-I
authors.initials: HI
authors.lastname: Yeh
authors.forename: Ping-Ying
authors.initials: PY
authors.lastname: Lee
authors.forename: Cheng-Huang
authors.initials: CH
authors.lastname: Su
authors.forename: Tin-Yi
authors.initials: TY
authors.lastname: Tian
authors.forename: Yu-Shien
authors.initials: YS
authors.lastname: Ko
authors.forename: Cheng-Ho
authors.initials: CH
authors.lastname: Tsai
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001262:Atenolol / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002478:Cells, Cultured; D018031:Connexin 43 / Q000096:biosynthesis*; D017630:Connexins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D011412:Propanolamines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016896:Treatment Outcome; D014471:Umbilical Veins / Q000378:metabolism / Q000473:pathology; D000097006:Gap Junction alpha-4 Protein
chemical_list: D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D015415:Biomarkers; D002227:Carbazoles; D000077261:Carvedilol; D018031:Connexin 43; D017630:Connexins; D019331:NG-Nitroarginine Methyl Ester; D011412:Propanolamines; D000097006:Gap Junction alpha-4 Protein