Takeshi Otsuki

Effects of leg resistance training on arterial function in older men

Background: Little information is available on the effect of strength training on vascular function, particularly in older people. Objective: To determine the effect of resistance training on arterial stiffness and endothelial function in older adults. Method: Eleven healthy men (mean (SEM) age 64 (1) years) performed 12 weeks of resistance training involving knee flexion and extension (three sets a day, two days a week). Results: Resistance training increased maximal muscle power by 16% (p<0.0001). Arterial stiffness as assessed by aortic pulse wave velocity did not change with resistance training. Plasma concentration of nitric oxide (NO), measured as its stable end product (nitrite/nitrate), had increased (p<0.05) after resistance training (61.2 (10.4) v 39.6 (3.2) μmol/l). There was no change in plasma concentration of endothelin-1. Conclusion: The results suggest that short term resistance training may increase NO production without stiffening central arteries in healthy older men.

Involvement of endothelin-1 in habitual exercise-induced increase in arterial compliance.

Aim:u2002 Habitual aerobic exercise results in a significant increase in central arterial compliance. Endothelin‐1 (ET‐1) is a potent endothelium‐derived vasoconstrictor peptide and could play a role in mediating the habitual aerobic exercise‐induced increase in central arterial compliance. The aim of the present study was to examine whether ET‐1 is involved in the mechanisms underlying the increase in central arterial compliance with aerobic exercise training.

Effect of systemic nitric oxide synthase inhibition on arterial stiffness in humans.

Stiffening of large elastic arteries impairs the buffering function of the arterial system and contributes to cardiovascular disease. The aim of this study was to determine whether endothelium-derived nitric oxide (NO) modulates the stiffness of large elastic arteries in humans. Seven apparently healthy adults (60±3 years, 2 males and 5 females) underwent systemic α-adrenergic blockade (phentolamine) and systemic NO synthase inhibition using NG-monomethyl-L-arginine (L-NMMA) in sequence. Phentolamine was given first to isolate contribution of NO to arterial stiffness by preventing reflex changes in sympathetic tone that result from systemic NO synthase inhibition, and also to compare arterial stiffness at a similar mean arterial pressure. Mean arterial blood pressure decreased (p<0.05) after phentolamine infusion but returned to baseline levels after L-NMMA infusion. The carotid β-stiffness index (via simultaneous ultrasound and applanation tonometry on the common carotid artery) did not change after the restraint of systemic α-adrenergic nerve activity (9.8±1.2 vs. 9.1±1.1 U) but increased (p<0.05) after NO synthase inhibition (12.6±2.0 U). These results suggest that NO appears to modulate central arterial stiffness in humans.

Reduction in α-adrenergic receptor-mediated vascular tone contributes to improved arterial compliance with endurance training

BACKGROUNDnRegular aerobic exercise improves large artery compliance in middle-aged and older humans. However, the underlying mechanisms are unknown. We tested the hypothesis that the improved central arterial compliance with endurance training is mediated by decreased alpha-adrenergic tone and/or increased endothelial function.nnnMETHODSnSeven sedentary healthy adults (60+/-3 years) underwent systemic alpha-adrenergic blockade (phentolamine) and nitric oxide synthase (NOS) inhibition using N(G)-monomethyl-L-arginine in sequence before and after a 3-month moderate endurance training (walk/jog, 4-5 days/week). Phentolamine was given first to isolate the contribution of nitric oxide to arterial compliance by minimizing reflex suppression of sympathetic tone resulting from systemic NOS inhibition as well as to assess the alpha-adrenergic receptor-mediated modulation of arterial compliance.nnnRESULTSnBaseline arterial compliance (via simultaneous ultrasound and applanation tonometry on the carotid artery) increased 34+/-12% after exercise training (P<0.01). When alpha-adrenergic blockade was performed, arterial compliance increased 37+/-6% (P<0.01) before the exercise training but did not change significantly after the training. Decreases in arterial compliance from the alpha-adrenergic blockade to the subsequent additional NOS blockade were not different before and after exercise training.nnnCONCLUSIONnOur results suggest that the reduction in alpha-adrenergic receptor-mediated vascular tone contributes to the improved central arterial compliance with endurance training.

Contribution of systemic arterial compliance and systemic vascular resistance to effective arterial elastance changes during exercise in humans

Background:u2002 Effective arterial elastance (Ea), an index of arterial load, increases with elevations in left ventricular elastance to maximize the efficiency of left ventricular stroke work during exercise. Systemic arterial compliance (C) and vascular resistance (R) are the primary components contributing to Ea, and R plays a greater role in determining Ea at rest. We hypothesized that the contribution of C to Ea increases during exercise to maintain an optimal balance between arterial load and ventricular elastance, and that the increase in Ea is due primarily to a reduction in C.

Weight Loss Reduces Plasma Endothelin-1 Concentration in Obese Men

Obesity is associated with endothelial dysfunction that may contribute to the development of diabetes, hypertension, and atherosclerosis. Endothelin-1 (ET-1), which is produced mostly by vascular endothelial cells, has potent vasoconstrictor and proliferative activity in vascular smooth muscle cells and, therefore, has been implicated in regulation of vascular tonus and the progression of atherosclerosis, suggesting that ET-1 may be important in endothelial dysfunction. We studied whether diet-induced weight loss (i.e., lifestyle modification) affects plasma ET-1 concentration in obese individuals. We measured plasma ET-1 concentration in seven obese men (age: 48 ± 4 years old, body mass index: 27.7 ± 0.5 kg/m2) before and after a 3-month, diet-induced weight reduction program (i.e., lifestyle modification program). Caloric restriction reduced body weight from 78 ± 3 to 68 ± 2 kg (P < 0.001) and resulted in 12.1 ± 1.2% reduction in body mass index (24.3 ± 0.3 kg/m2, P < 0.0001). After the weight reduction program, systolic and diastolic blood pressure significantly decreased (128 ± 7 vs. 115 ± 4 mm Hg, P < 0.05 and 88 ± 4 vs. 77 ± 2 mm Hg, P < 0.01, respectively). The plasma level of ET-1 significantly decreased after the program (5.1 ± 0.4 vs. 4.0 ± 0.3 pg/ml, P < 0.05). The percentage systolic blood pressure reduction and percentage plasma ET-1 concentration reduction was in a linear relationship (r = 0.86, P < 0.05). Furthermore, the relationship between percentage weight reduction and percentage plasma ET-1 concentration reduction was linear (r = 0.87, P < 0.05). We conclude that weight loss by low-calorie diet (i.e., lifestyle modification) reduces plasma ET-1 concentration in obese individuals. This reduction may contribute to the improvement of obesity-induced endothelial dysfunction.

Systemic arterial compliance, systemic vascular resistance, and effective arterial elastance during exercise in endurance-trained men

Systemic arterial compliance (C) and vascular resistance (R) regulate effective arterial elastance (Ea), an index of artery load. Increases in Ea during exercise are due primarily to reductions of C and maintain optimal ventricular-arterial coupling. Because C at rest and left ventricular functional reserve are greater in endurance-trained (ET) compared with sedentary control (SC) humans, we hypothesized that reductions of C and increases in Ea are greater in ET than SC individuals. The aim of this study was to investigate C, R, and Ea during exercise in ET and SC humans. C, R, Ea, and cardiac cycle length (T) were measured at rest and during exercise of 40, 60, and 80% maximal oxygen uptake using Doppler ultrasonography in 12 SC and 13 ET men. C decreased in an exercise intensity-dependent manner in both groups, but its reductions were greater in the ET than SC subjects. Consequently, although C at rest was greater in the ET than SC group, the intergroup difference in C disappeared during exercise. Exercise-related changes in R/T were relatively slight and R/T was lower in the ET than the SC group, both at rest and during exercise. Although Ea at rest was lower in the ET than SC group, there were no intergroup differences in Ea at 40, 60, or 80% maximal oxygen uptake. We conclude that the reductions of C from rest to exercise are more marked in ET than SC humans. This may be related to the exercise-associated disappearance of the difference in Ea between ET and SC humans.

Acute exercise increases systemic arterial compliance after 6-month exercise training in older women.

High physical activity or aerobic exercise training increases central arterial distensibility in older humans. However, the effect of a single bout of exercise on central arterial distensibility in older humans is unknown. Furthermore, the effect of exercise training on central arterial distensibility during exercise is unclear. We investigated whether systemic arterial compliance (SAC) changes after acute exercise in older humans, and, if so, whether this change in SAC is enhanced by aerobic exercise training. Seven untrained older women (61–69 years old) participated in a 6-month exercise intervention study. We measured SAC after acute exercise (cycling exercise at 80% of their individual ventilatory threshold for 30 min) before and after 6 months of aerobic exercise training. After exercise training, the individual ventilatory threshold was significantly increased. In addition, both the SAC at rest and that 30 min after acute exercise were significantly increased after the exercise training program. Before exercise training, there was no significant increase in SAC after acute exercise, whereas, after exercise training, the SAC was significantly increased 30 min after acute exercise. The present study suggests that, after aerobic exercise training, SAC increases after acute exercise in older humans, and that the SAC at rest and after acute exercise is enhanced by aerobic exercise training, thereby causing an effective adaptation in increase in cardiac output during exercise.

Arterial stiffness, physical activity, and atrial natriuretic Peptide gene polymorphism in older subjects.

An increase in arterial stiffness with advancing age is associated with several pathological states, including hypertension and arteriosclerosis. Regular exercise improves the aging-induced increase in arterial stiffness and has a protective effect against these diseases. However, not all individuals respond to exercise to the same extent. Atrial natriuretic peptide (ANP) is involved in the regulation of basal blood pressure, blood flow, and vascular tone. The present study was designed to clarify whether gene polymorphisms in ANP-related genes affect exercise-induced improvements in arterial stiffness. We performed a cross-sectional study of 291 healthy middle-aged and older Japanese subjects (63±1 years), examining the relationship between daily physical activity–induced improvements in arterial stiffness, estimated by brachial-ankle arterial pulse wave velocity (baPWV), and the gene polymorphisms of valine32methionine (V32M: 664G>A) in exon 1 of ANP and asparagine521aspartic acid (N521D: 1780A>G) in exon 8 of the ANP clearance receptor (NPR-C). The baseline baPWV was significantly lower in the active group, but no differences were seen in blood pressure. Active subjects with the ANP-VV genotype had significantly lower baPWV and higher plasma ANP levels compared with inactive subjects, but there were no variations related to the VM+MM genotype. Additionally, baPWV and plasma ANP levels were negatively correlated in ANP-VV genotype subjects, but were not correlated in VM+MM individuals. Our results suggest that ANP polymorphism in older Japanese subjects may affect the cardiovascular response to regular exercise.

Age-related reduction of systemic arterial compliance relates to decreased aerobic capacity during sub-maximal exercise.

A decrease in systemic arterial compliance (SAC) increases left ventricular load along with the demand for excessive myocardial oxygen consumption when the age-related reduction of SAC reaches a marked level, and consequently may depress left ventricular pump function. Reduced left ventricular pump function decreases aerobic capacity, and some study groups have shown that SAC and/or central arterial distensibility is correlated with maximal aerobic capacity in humans. We thus hypothesize that, once the age-related reduction of SAC reaches a marked level, the participation of SAC in aerobic capacity will be significant even during sub-maximal exercise. Thirty young humans and 46 elderly humans participated in this study. SAC, oxygen uptake at the ventilatory threshold ([Vdot ]O2 VT), and the ratio of increase in oxygen uptake, in cardiac output, and in effective arterial elastance to increase in work rate (Δ[Vdot ]O2/ΔWR, ΔCO/ΔWR and ΔEa/ΔWR) were measured. SAC was significantly higher in young subjects compared with elderly subjects, and was significantly related to [Vdot ]O2 VT in elderly subjects. SAC also significantly correlated with Δ[Vdot ]O2/ΔWR, ΔCO/ΔWR and ΔEa/ΔWR in elderly subjects. When total subjects were divided by the value of SAC into 6 groups, the [Vdot ]O2 VT values in the 3 groups with lower SAC were significantly lower than those in the 3 groups with higher SAC, and gradually decreased with the reduction of SAC. There were no changes in [Vdot ]O2 VT among the 3 groups with higher SAC. These results suggest that the participation of SAC in aerobic capacity is significant even during sub-maximal exercise in individuals who show a pronounced age-related reduction of SAC.