Estrogen and asymmetric dimethylarginine in postmenopausal women.

Postmenopausal Women To the Editor: We read with great interest the recent article by Holden et al1 dealing with the relationship between estrogen and asymmetric dimethylarginine (ADMA) metabolism in postmenopausal women. The results of their study demonstrated that hormone replacement therapy significantly decreased plasma ADMA levels in postmenopausal women. In an in vitro study, Holden et al1 observed that estrogen increased the activity of dimethylarginine dimethylaminohydrolase activity in endothelial cells. They proposed that estrogen can alter the catabolism and release of ADMA, which might partially contribute to the positive effect of estrogen on NO synthesis. Several studies have already reported that ADMA might have a crucial role in cardiovascular regulations. It was demonstrated that inhibition of NO bioavailability by ADMA and a subsequent reduction in endothelial function might contribute to the increase in blood pressure during salt intake in normotensive postmenopausal women not receiving estrogen.2 Similarly, it was reported that there was a significant inverse correlation between plasma ADMA and flow-mediated dilatation of brachial artery, indicating that ADMA might be related to a decline in endothelial vasodilator function.3 In a previous study, we showed that estrogen-induced improvement of membrane fluidity of erythrocytes was mediated by NO production, which was counteracted by ADMA in postmenopausal women.4 The finding suggests that ADMA might actively participate in the regulation of cell membrane function in postmenopausal women. Because the deformability and microviscosity of erythrocyte membranes may be highly dependent on the membrane fluidity, the reduction in membrane fluidity could cause a disturbance in the blood rheological behavior and in the microcirculation, which might contribute to the pathophysiology of hypertension. Recently, Achan et al5 demonstrated that intravenous infusion of ADMA increased blood pressure and systemic vascular resistance and decreased heart rate and cardiac output in humans. Therefore, we would like to know whether the hormone replacement therapy–induced decrease in plasma ADMA level might be accompanied by the changes in blood pressure and cardiac function. It would be important to assess more precisely whether ADMA may be involved in the cardiovascular disorders in postmenopausal women.