Hormone therapy modulates ET(A) mRNA expression in the aorta of ovariectomised New Zealand White rabbits

OBJECTIVE: To study the effect of 17beta-estradiol (E(2)) or conjugated equine estrogens (CEE) alone and in combination with norethisterone acetate (NETA) or medroxyprogesterone acetate (MPA) on the endothelin-1 (ET-1) system. METHODS: New Zealand White rabbits were treated with E(2), CEE, E(2) + NETA, CEE + MPA or placebo. The thoracic aorta and the epicardial coronary artery were used for mRNA expression and myograph analyses, respectively. RESULTS: E(2) and CEE alone significantly reduced ET-1 receptor subtype A (ET(A)) mRNA expression compared with placebo treatment. The E(2)-induced reduction in ET(A) mRNA expression persisted with the co-administration of NETA, but the CEE induced reduction in ET(A) mRNA expression was not maintained with the co-administration of MPA. Treatment with CEE alone significantly increased endotelin-1 converting enzyme (ECE) mRNA expression and CEE combined with MPA reduced prepro-endothelin-1 (ppET-1) mRNA expression when compared with placebo. ET-1 receptor subtype B mRNA expression and ET-1 induced vasocontraction was unaffected by treatment. CONCLUSIONS: E(2) and CEE treatment exert potentially beneficial vascular effects through regulation of the ET(A) receptor. The effect was maintained with the co-administration of NETA, but not MPA. The differential effects of specific hormone components may explain the variable effects of hormone therapy on the arterial wall.