Medroxyprogesterone acetate attenuates long-term effects of 17beta-estradiol in coronary arteries from hyperlipidemic rabbits
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Medroxyprogesterone acetate attenuates long-term effects of 17beta-estradiol in coronary arteries from hyperlipidemic rabbits. / Pedersen, Susan H; Nielsen, Lars Bo; Mortensen, Alicja; Sheykhzade, Majid; Nilas, Lisbeth; Ottesen, Bent.
In: Steroids, Vol. 71, No. 9, 09.2006, p. 834-42.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Medroxyprogesterone acetate attenuates long-term effects of 17beta-estradiol in coronary arteries from hyperlipidemic rabbits
AU - Pedersen, Susan H
AU - Nielsen, Lars Bo
AU - Mortensen, Alicja
AU - Sheykhzade, Majid
AU - Nilas, Lisbeth
AU - Ottesen, Bent
PY - 2006/9
Y1 - 2006/9
N2 - 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.CONCLUSION: 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.
AB - 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.CONCLUSION: 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.
KW - Animals
KW - Base Sequence
KW - Cholesterol/analysis
KW - Coronary Vessels/drug effects
KW - Estradiol/pharmacology
KW - Estrogen Replacement Therapy
KW - Female
KW - Hyperlipidemias/drug therapy
KW - Medroxyprogesterone Acetate/pharmacology
KW - Molecular Sequence Data
KW - Organ Size
KW - Ovariectomy
KW - Rabbits
KW - Time Factors
U2 - 10.1016/j.steroids.2006.05.014
DO - 10.1016/j.steroids.2006.05.014
M3 - Journal article
C2 - 16815506
VL - 71
SP - 834
EP - 842
JO - Steroids
JF - Steroids
SN - 0039-128X
IS - 9
ER -
ID: 272598251