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Hormone therapy modulates ETA mRNA expression in the aorta of ovariectomised New Zealand White rabbits

Objective. To study the effect of 17β-estradiol (E2) 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 E2, CEE, E2 + NETA, CEE + MPA or placebo. The thoracic aorta and the epicardial coronary artery were used for mRNA expression and myograph analyses, respectively. Results. E2 and CEE alone significantly reduced ET-1 receptor subtype A (ETA) mRNA expression compared with placebo treatment. The E2-induced reduction in ETA mRNA expression persisted with the co-administration of NETA, but the CEE induced reduction in ETA 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. E2 and CEE treatment exert potentially beneficial vascular effects through regulation of the ETA 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.