Sex hormones and asymmetric dimethylarginine in transplant arteriosclerosis.

in Transplant Arteriosclerosis To the Editor: We read with interest the recent article by Dr Weis and colleagues1 dealing with the role of asymmetric dimethylarginine (ADMA), the endogenous inhibitor of NO synthase, in arteriosclerosis in heart transplant recipients. The results of their study demonstrated that plasma ADMA is elevated in cardiac transplant recipients. In addition, the authors indicated that transplant recipients who are actively infected with cytomegalovirus have higher plasma ADMA levels and are at greater risk of transplant arteriosclerosis, because, in an in vitro study, endothelial cells infected by cytomegalovirus elaborated more ADMA and manifested an impairment of NO activity. The authors proposed that ADMA-induced endothelial dysfunction may play an important role in the altered vascular function and structure observed in the coronary arteries of cardiac transplant recipients. There is evidence that sex hormones might have a role in the ADMA-mediated regulation of cardiovascular functions. Holden et al2 showed that hormone replacement therapy significantly decreased plasma ADMA levels in postmenopausal women. They also observed that estrogen increased the activity of dimethylarginine dimethylaminohydrolase (DDAH) activity in endothelial cells and proposed that estrogen can alter the catabolism and release of ADMA. 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.3 In a previous study, we showed that estrogen-induced improvement of membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes is mediated by NO production, which is counteracted by ADMA in postmenopausal women.4 The finding suggests that, because abnormalities in membrane microviscosity could cause a disturbance in rheological behavior and microcirculation, estrogen deficiency with a concomitant increase in plasma ADMA levels might be involved in the pathogenesis of vascular complications in women. Recently, the role of estrogen in male physiology has also become evident, and normal physiological estrogen, which is converted from testosterone by aromatase, may confer cardiovascular benefits for men.5 In this context, we speculate that changes in sex hormones might modify the ADMA levels and cardiovascular complications in transplant recipients. Therefore, we would like to know the status of endogenous sex hormones in transplant recipients presented by Dr Weis and colleagues. It would be important to assess more precisely the relationship among sex hormones, ADMA, and arteriosclerosis in transplant recipients.