Effects of estrogen replacement therapy on natriuretic peptides and blood pressure.

Objective: Estrogen replacement therapy (ERT) has been reported to affect blood pressure. Since natriuretic peptides have natriuretic and vasodilatory activity and also inhibit the renin-angiotensin-aldosterone system and lower blood pressure, it was hypothesized that the changes in blood pressure effected by ERT might be mediated via changes in natriuretic peptides.

Methods: Fifty-eight postmenopausal hysterectomized women were randomized in a double-blind, double-dummy study to receive either peroral estradiol valerate 2 mg/day or transdermal estradiol gel containing 1 mg estradiol/day for 6 months. Blood pressure was measured by using an automatic, oscillometric device. Plasma atrial natriuretic peptide (ANP), N-terminal fragment of proANP (NT-proANP), B-type natriuretic peptide (BNP), aldosterone, and renin were determined by radioimmunoassay.

Results: The mean decrease in diastolic blood pressure was -6 mmHg both in the peroral group (n = 26) (P = 0.002) and in the gel group (n = 27) (P = 0.001), and the corresponding decreases in systolic blood pressure were -4 mmHg (P = 0.070) and -7 mmHg (P = 0.028) in the sitting position. Plasma NT-proANP rose from 212 to 264 pmol/l (P = 0.001) on peroral ERT and from 240 to 292 pmol/l (P = 0.008) on transdermal ERT. No significant changes were observed in the plasma ANP, BNP, aldosterone, and renin levels.

Conclusions: Both peroral and transdermal ERT result in elevated plasma levels of NT-proANP, indicating an activation of the natriuretic peptide system. This could explain, at least in part, the lowering of blood pressure during ERT.