Aims: The Modelflow method can estimate cardiac output from arterial blood pressure waveforms using a three-element model of aortic input impedance (aortic characteristic impedance, arterial compliance, and systemic vascular resistance). We tested the reliability of a non-invasive cardiac output estimation during submaximal exercise using the Modelflow method from finger arterial pressure waveforms collected by Portapres in healthy young humans. Methods: The Doppler echocardiography method was used as a reference method. Sixteen healthy young subjects (nine males and seven females) performed a multi-stage cycle ergometer exercise at an intensity corresponding to 70, 90, 110 and 130% of their individual ventilatory threshold for 2 min each. The simultaneous estimation of cardiac output (15 s averaged data) using the Modelflow and Doppler echocardiography methods was performed at rest and during exercise. Results and Conclusion: The Modelflow-estimated cardiac output correlated significantly with the simultaneous estimates by the Doppler method in all subjects (r ¼ 0.87, P < 0.0001) and the SE of estimation was 1.93 L min )1 . Correlation coefficients in each subject ranged from 0.91 to 0.98. Although the Modelflow method overestimated cardiac output, the errors between two estimates were not significantly different among the exercise levels. These results suggest that the Modelflow method using Portapres could provide a reliable estimation of the relative change in cardiac output non-invasively and continuously during submaximal exercise in healthy young humans, at least in terms of the relative changes in cardiac output. Keywords cardiac output, Doppler echocardiography, finger arterial pressure waveform.Cardiac output (CO) is one indicator of cardiac function. A non-invasive estimation of CO with high time resonance is favourable in exercise physiological research. The Modelflow method involves the measurement of beat-by-beat aortic flow volume from arterial pressure waveforms (Wesseling et al.

Endothelial function deteriorates with aging. On the other hand, exercise training improves the function of vascular endothelial cells. Endothelin-1 (ET-1), which is produced by vascular endothelial cells, has potent constrictor and proliferative activity in vascular smooth muscle cells and, therefore, has been implicated in regulation of vascular tonus and progression of atherosclerosis. We previously reported significantly higher plasma ET-1 concentration in middle-aged than in young humans, and recently we showed that plasma ET-1 concentration was significantly decreased by aerobic exercise training in healthy young humans. We hypothesized that plasma ET-1 concentration increases with age, even in healthy adults, and that lifestyle modification (i.e., exercise) can reduce plasma ET-1 concentration in previously sedentary older adults. We measured plasma ET-1 concentration in healthy young women (21-28 yr old), healthy middle-aged women (31-47 yr old), and healthy older women (61-69 yr old). The plasma level of ET-1 significantly increased with aging (1.02 +/- 0.08, 1.33 +/- 0.11, and 2.90 +/- 0.20 pg/ml in young, middle-aged, and older women, respectively). Thus plasma ET-1 concentration was markedly higher in healthy older women than in healthy young or middle-aged women (by approximately 3- and 2-fold, respectively). In healthy older women, we also measured plasma ET-1 concentration after 3 mo of aerobic exercise (cycling on a leg ergometer at 80% of ventilatory threshold for 30 min, 5 days/wk). Regular exercise significantly decreased plasma ET-1 concentration in the healthy older women (2.22 +/- 0.16 pg/ml, P < 0.01) and also significantly reduced their blood pressure. The present study suggests that regular aerobic-endurance exercise reduces plasma ET-1 concentration in older humans, and this reduction in plasma ET-1 concentration may have beneficial effects on the cardiovascular system (i.e., prevention of progression of hypertension and/or atherosclerosis by endogenous ET-1).

Vascular endothelial cells produce nitric oxide (NO), which is a potent vasodilator substance and is thoughtto have antiatherosclerotic properties. Therefore, it has also been proposed that NO may be useful to regulate vascular tonus and prevent progression of atherosclerosis. On the other hand, NO activity reduces with aging. We previously reported that the plasma nitrite/nitrate (NOx: the stable end product of NO) concentration was significantly increased by intense aerobic exercise training in healthy young humans. We hypothesized that lifestyle modification (e.g., even mild regular exercise training) can increase NO production in previously sedentary older humans. We measured the plasma NOx concentration before and after a mild aerobic exer-

Exercise training improves aging-induced deterioration of angiogenesis in the heart. However, the mechanisms underlying exercise-induced improvement of capillary density in the aged heart are unclear. Vascular endothelial growth factor (VEGF) is implicated in angiogenesis, which activated angiogenic signaling cascade through Akt and endothelial nitric oxide synthase (eNOS)-related pathway. We hypothesized that VEGF angiogenic signaling cascade in the heart contributes to a molecular mechanism of exercise training-induced improvement of capillary density in old age. With the use of hearts of sedentary young rats (4 mo old), sedentary aged rats (23 mo old), and exercise-trained aged rats (23 mo old, swim training for 8 wk), the present study investigated whether VEGF and VEGF-related angiogenic molecular expression in the aged heart is affected by exercise training. Total capillary density in the heart was significantly lower in the sedentary aged rats compared with the sedentary young rats, whereas that in the exercise-trained rat was significantly higher than the sedentary aged rats. The mRNA and protein expressions of VEGF and of fms-like tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk-1), which are main VEGF receptors, in the heart were significantly lower in the sedentary aged rats compared with the sedentary young rats, whereas those in the exercise-trained rats were significantly higher than those in the sedentary aged rats. The phosphorylation of Akt protein and eNOS protein in the heart corresponded to the changes in the VEGF protein levels. These findings suggest that exercise training improves aging-induced downregulation of cardiac VEGF angiogenic signaling cascade, thereby contributing to the exercise training-induced improvement of angiogenesis in old age.

These results suggest that both moderate and vigorous physical activities have favorable effects on central arterial stiffness in postmenopausal women.