We assessed the influence of aging on cardiac function by means of parameters measured by echocardiography. The study group consisted of 494 normal subjects aged 13 to 87 years. We measured the ratio of early filling (E) and atrial contraction (A) transmitral flow velocities (E/A) of left and right ventricular inflow (LV E/A and RV E/A) for assessment of diastolic function. We also measured left ventricular ejection fraction (LVEF), and the ratio of pre-ejection period (PEP) and ejection time (ET) of the left ventricle (PEP/ET) for assessment of systolic function. Both LV E/A and RV E/A decreased significantly with aging while LVEF and PEP/ET remained normal range. The decline rate as aging was greater in LV E/A than in RV E/A. These results showed that both left and right ventricular diastolic function deteriorated with aging while left ventricular systolic function was not noticeably affected by aging. We suggest that indexes of diastolic function are more sensitive than those of systolic function when the natural course is studied in a large population.

In our previous study, we found that the vasodilation of retinal arterioles induced by acetylcholine and BMS-191011, a large-conductance Ca 2+ -activated K + (BK Ca ) channel opener, were diminished in diabetic rats. Currently, few agents ameliorate the impaired vasodilator responses of retinal blood vessels. Our recent finding that the intravenous infusion of L-citrulline dilated retinal arterioles, suggests that L-citrulline could be a potential therapeutic agent for circulatory disorders of the retina. In this study, we determined the effect of an oral L-citrulline treatment on impaired acetylcholine- and BMS-191011-induced vasodilation in the retinal arterioles of diabetic rats. To induce diabetes, rats were administered an intravenous dose of streptozotocin (65 mg/kg) and a 5% D-glucose solution as drinking water. The L-citrulline (2 g/kg/day) and L-arginine (2 g/kg/day) treatments commenced either 15 days before or just after the streptozotocin injection and continued throughout the experimental period. A 29-day treatment with L-citrulline, but not L-arginine, significantly ameliorated the impaired acetylcholine- and BMS-191011-induced retinal vasodilation in diabetic rats without affecting their plasma glucose levels. The 2-week L-citrulline treatment tended to ameliorate the dysfunction of the acetylcholine-induced retinal vasodilation in diabetic rats. In conclusion, these results showed that the retinal blood vessel dysfunction induced by diabetes mellitus could be prevented by the long-term administration of L-citrulline and suggest that the latter could play a potentially prophylactic role in diabetic retinopathy.