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

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Abstract
Changes in vascular nitric oxide (NO) activity may contribute to cardiovascular risk. We determined the effect of the menopause, gen- der, and estrogen replacement therapy on arterial vascular NO ac- tivity. 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 mg conjugated estrogens) were studied in 20 healthy postmenopausal women (60 yr). Forearm blood flow re- sponses to brachial arterial infusions of L-NG-monomethyl-arginine (L-NMMA), norepinephrine, glyceryl trinitrate (GTN), and serotonin were determined using venous occlusion plethysmography. Constric- tor responses to L-NMMA were reduced in postmenopausal women (82 6 14, summary response, mean 6 SEM) and men (89 6 6) compared to premenopausal women (118 6 10; P , 0.05). Constrictor responses to norepinephrine were increased in males (125 6 13) compared to premenopausal (81 6 8) and postmenopausal (88 6 16) women (P , 0.05). No differences were observed in GTN or serotonin responsive- ness. Constrictor responses to L-NMMA increased after estrogen re- placement (132 6 7 vs. 89 6 14; P , 0.05), with no change in nor- epinephrine, 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 contrib- ute to changes in cardiovascular risk associated with male gender, postmenopausal status, and estrogen replacement therapy. Increased a-adrenoceptor responsiveness may contribute to increased cardio- vascular risk in males. (J Clin Endocrinol Metab 85: 1577-1583, 2000)

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