title: Hormone replacement therapy can augment vascular relaxation in post-menopausal women with type 2 diabetes.
abstract: BACKGROUND
  Diabetes is a major risk factor for coronary heart disease in women and event rates increase substantially after the menopause. Observational studies have suggested that estrogens may provide cardioprotection by regulating endothelial nitric oxide synthase.
  
  
  METHODS
  In order to examine the effect of hormone replacement therapy (HRT) on endothelium-dependent and -independent vascular relaxation in post-menopausal women with type 2 diabetes, an open study was conducted in which gluteal biopsies were collected from 17 women before and after 6 months of transdermal 17 beta-estradiol (80 microg twice weekly) in combination with oral norethisterone (1 mg daily). Small arteries (<550 microm) were dissected from fat and mounted on a wire myograph for assessment of relaxation in response to acetylcholine (ACh), bradykinin (BK) and sodium nitroprusside (SNP).
  
  
  RESULTS
  Maximal relaxation responses to ACh, BK and SNP in women with diabetes and non-diabetic control subjects were 52 +/- 8 versus 96 +/- 2% (P < 0.05), 76 +/- 7 versus 97 +/- 1%, (P < 0.05) and 91 +/- 2 versus 98 +/- 1% (P < 0.05) respectively. After 6 months of HRT, maximal relaxation responses to ACh, BK and SNP in women with diabetes (compared with pre-HRT) were: 88 +/- 4 (P < 0.05), 93 +/- 3 (P < 0.05) and 98 +/- 1% (P < 0.05) respectively. At baseline and after HRT, EC50 (concentration required to obtain 50% of maximum response) data exhibited similar changes.
  
  
  CONCLUSIONS
  HRT had potentially beneficial effects on vascular relaxation. Data were consistent with improvements in endothelial function, vascular smooth muscle function, or both. Controlled studies are required to confirm and extend these findings.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Glasgow, G3 8SJ, UK.
authors.forename: M
authors.initials: M
authors.lastname: Perera
authors.forename: J R
authors.initials: JR
authors.lastname: Petrie
authors.forename: C
authors.initials: C
authors.lastname: Hillier
authors.forename: M
authors.initials: M
authors.lastname: Small
authors.forename: N
authors.initials: N
authors.lastname: Sattar
authors.forename: J M C
authors.initials: JM
authors.lastname: Connell
authors.forename: M A
authors.initials: MA
authors.lastname: Lumsden
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002081:Buttocks / Q000098:blood supply; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004958:Estradiol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D009640:Norethindrone / Q000627:therapeutic use; D017698:Postmenopause / Q000502:physiology*; D045167:Progesterone Congeners / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D045167:Progesterone Congeners; D014665:Vasodilator Agents; D009599:Nitroprusside; D004958:Estradiol; D000109:Acetylcholine; D001920:Bradykinin; D009640:Norethindrone