Effects of the Menopause, Gender, and Estrogen Replacement Therapy on Vascular Nitric Oxide Activity

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 4; pp. 1577 - 1583
• Main Authors: Majmudar, N. G., Robson, S. C., Ford, G. A.
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01-04-2000
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.85.4.6530

Changes in vascular nitric oxide (NO) activity may contribute to
cardiovascular risk. We determined the effect of the menopause, gender,
and estrogen replacement therapy on arterial vascular NO activity.
Vascular NO activity and sensitivity were determined in 15 healthy
premenopausal women (mean age, 48 yr), 12 postmenopausal women (51 yr),
and 14 men (51 yr). The effects of 14 days of estrogen replacement
therapy (625 μg conjugated estrogens) were studied in 20 healthy
postmenopausal women (60 yr). Forearm blood flow responses to brachial
arterial infusions of
l-NG-monomethyl-arginine
(L-NMMA), norepinephrine, glyceryl trinitrate (GTN), and
serotonin were determined using venous occlusion plethysmography.
Constrictor responses to L-NMMA were reduced in postmenopausal women
(82 ± 14, summary response, mean ± sem) and men
(89 ± 6) compared to premenopausal women (118 ± 10;
P < 0.05). Constrictor responses to norepinephrine
were increased in males (125 ± 13) compared to premenopausal
(81 ± 8) and postmenopausal (88 ± 16) women
(P < 0.05). No differences were observed in GTN or
serotonin responsiveness. Constrictor responses to L-NMMA increased
after estrogen replacement (132 ± 7 vs. 89 ±
14; P < 0.05), with no change in norepinephrine,
GTN, or serotonin responses. The menopause and male gender were
associated with reduced arterial NO activity. Two weeks of estrogen
replacement therapy restored vascular NO activity to premenopausal
levels. Changes in vascular NO activity may contribute to changes in
cardiovascular risk associated with male gender, postmenopausal status,
and estrogen replacement therapy. Increased α-adrenoceptor
responsiveness may contribute to increased cardiovascular risk in
males.