Upregulation of the Nitric Oxide-cGMP Pathway in Aged Myocardium

To the Editor: Zieman et al1 recently assessed the effect of age on the cardiac NO-cGMP pathway postulating that, since NO promotes ventricular relaxation, a reduction in functional NO activity may explain the increased ventricular diastolic dysfunction associating with normal aging. Perhaps surprisingly, the authors observed that elderly male Wistar rats (22 to 25 months old) showed higher constitutive cardiac NOS activity and cardiac endothelial nitric oxide synthase (eNOS) levels than young adult rats (4 to 7 months). Much of this increased activity appeared to take place in the cardiac endothelium rather than the myocytes. The authors concluded that the age-related impairment of ventricular relaxation is mediated by mechanisms other than …