title: Progestins used in hormonal replacement therapy display different effects in coronary arteries from New Zealand white rabbits.
abstract: OBJECTIVE
  The aim of this study was in an animal model to assess the vascular effects of different progestins commonly used in hormonal replacement treatment.
  
  
  METHODS
  Fifty-six non-atherosclerotic, ovariectomized New Zealand white rabbits were randomized into seven groups: (1) medroxyprogesterone acetate (MPA), (2) norethisterone acetate (NETA), (3) conjugated equine estrogens (CEE), (4) 17-beta-estradiol (E2), (5) MPA+CEE , (6) NETA+E2 , (7) or placebo (n=8) and given hormonal treatment through the diet for 4 weeks. Ring segments from the left proximal coronary artery and from the distal part of the left anterior descending coronary artery were microdissected and mounted for isometric tension recordings in a myograph. The vasoconstrictory responses induced by potassium, endothelin-1, calcium and Nw-nitro-L-arginine methyl ester, and the vasodilatory response induced by acetylcholine and sodiumnitroprusside were investigated. The maximum contraction/relaxation (Emax) and the concentration required to induce half the maximum response (EC50) were determined. EC50 values were expressed as the negative logarithm to the molar concentration, pD2=-log EC50.
  
  
  RESULTS
  Treatment with MPA alone caused when compared to treatment with NETA an increase in tension development in the distal coronary artery after the addition of potassium ( 6.36+/-0.36 versus 4.31+/-0.42 P<0.005) (single dose response, mN/mm, mean+/-S.E.M.) and endothelin-1 (9.41+/-0.82 versus 6.43+/-0.73 P<0.05) (Emax, mN/mm, mean+/-S.E.M.). Treatment with MPA compared to placebo caused an endothelin-1 induced increase of Emax in the distal coronary artery (9.21+/-0.87 versus 6.51+/-0.65 P<0.05) and a calcium induced increase of pD2 in both coronary arteries (2.98+/-0.19 versus 2.42+/-0.12 P<0.05, proximal coronary artery) (3.26+/-0.09 versus 2.9+/-0.1 P<0.05, distal coronary artery) (pD2, mean+/-S.E.M.). Treatment with NETA compared to placebo in the proximal coronary artery, after the addition of sodiumnitroprusside caused a decrease of pD2 (5.33+/-0.19 versus 5.94+/-0.13 P<0.05). Treatment with E2 compared to treatment with CEE in the proximal coronary artery caused a decrease of pD2 after the addition of sodiumnitroprusside (5.00+/-0.16 versus 5.77+/-0.28 P<0.05). No significant differences were found between MPA+CEE and NETA+E2.
  
  
  CONCLUSIONS
  Treatment with MPA alone seems to enhance the contractile response to potassium and endothelin-1 in the distal coronary artery compared to NETA, indicating that different progestins used in hormonal replacement treatment may display different effects on contractile functions of coronary arteries.
authors.affiliation: Department of Obstetrics and Gynaecology, Clinical Research Unit, Hvidovre University Hospital, Copenhagen, Denmark.
authors.forename: Nina G
authors.initials: NG
authors.lastname: Pedersen
authors.forename: Susan H
authors.initials: SH
authors.lastname: Pedersen
authors.forename: Tórur
authors.initials: T
authors.lastname: Dalsgaard
authors.forename: Claus O
authors.initials: CO
authors.lastname: Lund
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Nilas
authors.forename: Bent
authors.initials: B
authors.lastname: Ottesen
mesh_terms: D000109:Acetylcholine; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium; D003331:Coronary Vessels / Q000187:drug effects*; D004195:Disease Models, Animal; D019332:Endothelin-1; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008593:Menopause; D019331:NG-Nitroarginine Methyl Ester; D009599:Nitroprusside; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D010052:Ovariectomy; D011188:Potassium; D011372:Progestins / Q000494:pharmacology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D004966:Estrogens, Conjugated (USP); D011372:Progestins; D009599:Nitroprusside; D004958:Estradiol; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D009640:Norethindrone; D019331:NG-Nitroarginine Methyl Ester