Asymmetric dimethylarginine and circulatory disorders in postmenopausal women.

Disorders in Postmenopausal Women To the Editor: We read with great interest the recent article by Dr Stühlinger et al1 dealing with the relationship among asymmetric dimethylarginine (ADMA), homocyst(e)ine, and endothelial function in young healthy adults, patients with peripheral arterial disease, and older healthy adults. The results of their study demonstrated that experimentally induced hyperhomocyst(e)inemia increased plasma ADMA, an effect that was temporally related to a decline in endothelial vasodilator function. Dr Stühlinger et al1 proposed that ADMA might have a causal role in endothelial dysfunction because there was a significant inverse correlation between plasma ADMA and flow-mediated dilatation of the brachial artery. Several studies have already reported that endothelial function was strongly influenced by estrogen status and was restored by estrogen replacement therapy in postmenopausal women.2 In a separate series of the study, Dr Stühlinger and colleagues3 showed that inhibition of nitric oxide (NO) bioavailability by ADMA and a subsequent reduction in endothelial dysfunction might contribute to the increase in blood pressure during salt intake in normotensive postmenopausal women not receiving estrogen. It was also demonstrated that estrogen replacement therapy significantly reduced plasma concentration of ADMA in postmenopausal women.4 In a study we presented earlier, it was shown that estrogen-induced improvement of membrane fluidity (the reciprocal value of microviscosity) of erythrocytes was counteracted by ADMA, suggesting that NO might actively participate in the regulation of rheologic behavior of cell membranes and microcirculation in postmenopausal women.5 In this context, it can be speculated that, in postmenopausal women with higher ADMA levels, the circulatory disorders are more pronounced. The precise mechanisms responsible for the increased ADMA in cardiovascular events in women are still unclear. It is possible that estrogen deficiency after menopause might accelerate abnormalities in endothelial function by increasing ADMA levels. Although only 3 female patients were enrolled in the present study of Dr Stühlinger et al,1 it would be important to explore the gender difference of ADMA kinetics and further to assess more precisely whether the higher ADMA may be associated with increased cardiovascular diseases in elderly women.