Medroxyprogesterone acetate attenuates long-term effects of 17beta-estradiol in coronary arteries from hyperlipidemic rabbits.
OBJECTIVE
The progestin component in hormone replacement treatment may oppose the effects of estrogen on vascular function. This study examined the effect of long-term treatment with 17beta-estradiol (E(2)) alone and in combination with two progestins on K(+) and Ca(2+)-mediated mechanisms in coronary arteries.


METHODS
Watanabe heritable hyperlipidemic rabbits were treated orally with either E(2) (4 mg/day), medroxyprogesterone acetate (MPA) (10 mg/day), norethindrone acetate (NETA) (2 mg/day), E(2)+MPA, E(2)+NETA, or placebo for 16 weeks (n=10 in each group). Coronary arteries were used for mRNA and myograph studies.


RESULTS
E(2) increased vasodilatation induced by sodium nitroprusside and decreased vasocontraction induced by potassium. The first but not the latter response was opposed by MPA. The combination of MPA and E(2), but neither compound alone enhanced nimodipine-induced vasodilatation and increased the expression of L-type voltage-gated Ca(2+) channel mRNA. NETA had no opposing effects. Hormone treatment did not affect large-conductance Ca(2+) activated or ATP-sensitive K(+) channels or cGMP-dependent protein kinase mRNA expression. Hyperlipidemia had no effect on vascular reactivity.


CONCLUSIONS
When E(2) is administered with MPA, effects of E(2) on nitric oxide and Ca(2+)-mediated vascular reactivity in rabbit coronary arteries are modulated. The results suggest that the progestin component in hormone replacement treatment may interfere with the supposed beneficial vascular effects of estrogen.
Pedersen
Susan H
SH
The Juliane Marie Centre, Copenhagen University Hospital, Denmark. susanpedersen@dadlnet.dk
Nielsen
Lars Bo
LB
Mortensen
Alicja
A
Sheykhzade
Majid
M
Nilas
Lisbeth
L
Ottesen
Bent
B
D000818:Animals; D001483:Base Sequence; D002784:Cholesterol / Q000032:analysis; D003331:Coronary Vessels / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006949:Hyperlipidemias / Q000188:drug therapy*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology* / Q000627:therapeutic use; D008969:Molecular Sequence Data; D009929:Organ Size; D010052:Ovariectomy; D011817:Rabbits; D013997:Time Factors
D004958:Estradiol; D002784:Cholesterol; D017258:Medroxyprogesterone Acetate