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Matsuda, M. Review : Aging and Health Promotion Effects of Exercise and Physical Activity on Prevention of Arteriosclerosis ― Special Reference to Arterial Distensibility ― Mitsuo Matsuda*,** * Tsukuba Advanced Research Alliance, University of Tsukuba 1-1-1 Tennodai, Tsukuba-shi, Ibaraki 305-8577, Japan email@example.com ** Tsukuba Indaustrial Liason and Cooperative Center, University of Tsukuba [Received May 20, 2005 ; Accepted November 7, 2005] Arterial distensibility, particularly central arterial distensibility, decreases with age-related changes in the arterial wall and, as a result, systolic blood pressure and/or pulse pressure (difference of systolic pressure and diastolic pressure) may increase in the elderly. Systolic hypertension, increased pulse pressure, and decreased central arterial distensibility are known to be independent risk factors for cardiovascular and cerebrovascular diseases. Decreased arterial distensibility may also cause the deterioration of physical ability in the elderly. Several previous studies, as well as the current investigation, have shown that daily physical activity is positively related to arterial distensibility in not only young but also elderly people and that relatively short-term and low-intensity aerobic exercise training could improve arterial distensibility even in the elderly. It has been shown, however, that the effect cannot be maintained without continued physical exercise. Some presumable biological mechanisms and the appropriate amount and/or intensity of physical activity and aerobic exercise for improving arterial distensibility have also been revealed. Thus, habitual physical activity and exercise may have the effect of retarding age-related changes to the arteries and establishing higher quality of life by preventing cardiovascular and cerebrovascular diseases and by improving physical ability in the elderly. Keywords: physical activity volume, exercise intensity, exercise training, systemic arterial compliance, pulse wave velocity, systolic blood pressure, pulse pressure [International Journal of Sport and Health Science Vol.4, 316-324, 2006] 1. Introduction in recent times, the top three causes of death for both males and females are cancer, cardiac diseases A statement released by the American Heart and cerebrovascular diseases. Among them, both Association (Thompson, et al., 2003) reported that ischemic heart diseases and cerebrovascular diseases aerobic exercise of moderate intensity performed are attributable to arteriosclerosis and combined they for 30 minutes or more per day (relevant to relative are the leading cause of death in Japan. In addition, intensity of 40-60 % of maximal oxygen uptake, or stroke due to cerebrovascular diseases is the major absolute intensity of 4-6 METs: correspondence event that causes elderly people to become bedridden. to relative intensity should vary according to age Thus, it is presumed that there would be a positive (physical fi tness)) should be conducted on most, influence on health maintenance and enhancement and preferably all, days of the week in order to for middle-aged and elderly people in Japan if the prevent arteriosclerotic cardiovascular diseases occurrence of arteriosclerotic cardiovascular and and that medical services and healthcare experts cerebrovascular diseases is restricted by actively should personally engage in an active lifestyles to pursuing the goals set out in the statement made by familiarize themselves with the issues involved in the American Heart Association. maintaining lifelong physical activity and to set a Arteriosclerosis is classifi ed as arteriolar ooitive example for patients and the public. In Japan arteriosclerosis due to the degeneration of arteriole 316 International Journal of Sport and Health Science Vol.4, 316-324, 2006 http://www.soc.nii.ac.jp/jspe3/index.htm Prevention of Arteriosclerosis walls caused by aging, hypertension and diabetes, 2. The effects of exercise and physical atherosclerosis due to subintimal deposition of activity on the age-related decrease of arterial atheromas in large or medium-sized arteries and distensibility medial arteriosclerosis that occurs mainly in large artery media as age-related change. The effect of 2.1. Age-related change in artery and systolic aerobic exercise on the prevention of atherosclerotic hypertension disease has been proved by many epidemiological and experimental studies (Thompson, et al., 2003). Hypertension is the leading risk factor for stroke In fact, a strong quantitative correlation is observed and ischemic heart disease caused by arteriosclerosis. between habitual physical activity level and the In general, systolic blood pressure increases with age, risk of several chronic diseases, including coronary while diastolic blood pressure decreases (Franklin, artery disease and coronary risk factors, such as et al., 1997). Consequently, systolic hypertension hypertension, and non-insulin-dependent diabetes with associated pulse pressure increase is frequently mellitus, demonstrating a graded relationship of observed in middle-aged and elderly people. Systolic increasing risks of the diseases with decreasing levels hypertension, which was at one time underestimated of the physical activity. Several prospective studies as an aging phenomenon, is never innocent to the suggested that a decline in physical activity level human body. An increase in systolic blood pressure precedes the development of arteriosclerotic diseases and pulse pressure is known to be an independent risk and that the decline is not induced by the disease. factor for stroke and ischemic heart disease (Beneton Furthermore, the fact that regular exercise is effective A, et al., 1997). The occurrence rates of stroke and in reducing the risk of developing arteriosclerotic ischemic heart disease rise more clearly in patients diseases has been reported as well as the biological with even moderate systolic hypertension compared mechanism (i.e. beneficial effects on atherosclerotic to normotensive people (Sagie A, et al., 1993), while risk factor, myocardial function, coronary artery size it has been shown that a decline in systolic blood and vasodilatory capacity, vascular tone, fibrinolysis, pressure lowers the occurrence rates of stroke and platelet function, and vulnerability to ventricular ischemic heart disease considerably (Asia Pacifi c fibrillation) in many intervention and experimental Cohort Studies Collaboration, 2003). studies. A plausible and consistent relationship The major reason for the increase in systolic between physical activity and its preventive effect on blood pressure and pulse pressure with aging is that arteriosclerosis has been observed and consequently the buffering function of blood pressure and the it is estimated that there should be a causal bloodstream declines due to the decrease in arterial relationship between them. compliance caused by lesser extensibility with This paper will discuss the effect of exercise age-related changes in the wall of the large artery and physical activity on the decline in arterial (the central artery), such as the aorta (Nichols and distensibility, which is closely related to medial O’Rourke, 1998). That is, when the total systemic arteriosclerosis of large sized arteries, mainly arterial compliance decreases, as indicated in the based on the results of our study, which targeted formula C =ΔV/ΔP, arterial inner pressure rises in middle-aged and elderly people. The term ‘arterial a condition of a fixed cardiac output. In addition, distensibility’ is used as a generic term for the since the function of collecting blood ejected from physical value including arterial wall distensibility, the left ventricle by extending the artery wall is volume distensibility of tubular structure arteries restricted, blood pressure drops causing a decrease and arterial compliance. Arterial wall distensibility in bloodstream to peripheral vessels during the left (D) is the physical volume corresponding to the ventricular diastole after a rapid rise occurs in blood proportion between stress and strain per unit of length pressure during the left ventricular systole. The or unit of area of the arterial wall. In contrast, arterial contribution rate of the proximal aorta (ascending compliance (C) corresponds to the proportion (ΔV/ΔP) aorta and aortic arch) in systemic arterial compliance between the increase (ΔP) in intra-arterial pressure is about 60 % (Stergiopulos, et al., 1998) and the (P) and the increase (ΔV) in arterial volume (V). contribution rate of the central artery may become Therefore, there is the relation of D = C/V between larger than this as the descending, abdominal the arterial distensibility and arterial compliance. and carotid arteries are included. In terms of the International Journal of Sport and Health Science Vol.4, 316-324, 2006 317 http://www.soc.nii.ac.jp/jspe3/index.htm Matsuda, M. A B n=413 n=413 Systemic arterial compliance (ml/mmHg) (mmHg) r=0.30 r=0.41 3.0 220 Systolic blood pressure p<0.0001 p<0.0001 180 2.0 140 1.0 100 0 60 40 50 60 70 80 90 (years) 0 1.0 2.0 3.0 (ml/mmHg) Age Systemic arterial compliance (age adjusted value) Figure 1 The relationship between systemic arterial compliance and age (A), and the relationship between systemic arterial compliance (age adjusted value) and systolic blood pressure (B) relationship between systemic arterial compliance, people by Tanaka, et al. (2000). Moreover, Cameron, age and systolic blood pressure measured by us in et al. observed signifi cant positive correlation middle-aged and elderly people, it has been observed between systemic arterial compliance and duration that systemic arterial compliance decreases with of incremental exercise in middle-aged and elderly aging (Figure 1 A), and that a decrease in systemic people. However, all of these studies investigated the arterial compliance raises systolic blood pressure relationship between maximum exercise capability and (Figure 1 B). In some recent studies, it has been arterial distensibility. It is presumed that whole body elucidated that the decline itself in central artery endurance (aerobic) capacity in submaximal exercise distensibility can be an independent risk factor for is more meaningful than maximal physical capacity cardiovascular diseases in hypertension patients as to daily vital functions in the majority of middle-aged well as systolic hypertension (Blacher, et al., 1999, and elderly people. Thus we have examined the Laurent, et al., 2001). relationship between aerobic capacity and systemic arterial compliance in middle-aged and elderly people 2.2. Arterial distensibility and aerobic exercise during submaximal exercise, and clarified that aerobic capacity capacity (oxygen uptake at the ventilatory threshold level) is low in middle-aged and elderly people as Since an increase in systolic blood pressure due the value of systemic arterial compliance declines to the decline in arterial distensibility augments (Figure 2: Otsuki, et al., 2003), which means that the the burden on heart (afterload), and the decline in decline in distensibility of the central artery is one of diastolic blood pressure lessens the amount of blood the factors to restrict vital function in the every day flowing into the cardiac muscle, cardiac functions lives of middle-aged and elderly people. are suppressed (Urshel, et al., 1968). The decline in arterial distensibility with aging lessens the cardiac 2. 3. Arterial distensibility, exercise and function during exercise in particular, which might physical activity cause a decline in physical fitness (aerobic exercise capacity) (Nichols and O’Rourke, 1998). In fact, it has Arterial distensibility is higher in athletes who been suggested that there exists significant correlation continue high-aerobic exercise (Mohiaddin, et al., between the peak oxygen uptake or maximal oxygen 1989, Vaikevicius, et al., 1993, Kakiyama, et al., uptake and arterial distensibility in a wide range of age 1998a) and active people in general (Kakiyama, groups from youth to middle-aged and elderly people et al., 1998a, 1998b, Tanaka, et al., 2000, Tanabe, by Vaitkevicius, et al. (1993), in youth by Cameron et al., 2003a, 2004). The effect observed in and Dart (1994) and in middle-aged and elderly cross-sectional data does not necessarily indicate 318 International Journal of Sport and Health Science Vol.4, 316-324, 2006 http://www.soc.nii.ac.jp/jspe3/index.htm Prevention of Arteriosclerosis Tanabe, et al., 2003a, 2004), it is indicated ml/kg/min Aerobic exercise capacity (VO2@VT) 24 that physical activity volume can have the n=46 effect of decreasing systolic blood pressure r=0.4 signifi cantly by restricting the decline in 20 p<0.005 artery distensibility with aging. In addition, when examining the relationship between 16 physical activity volume and systemic arterial compliance in middle-aged and 12 elderly people, including those with a higher level of daily physical activity (such 8 as belonging to a "walking circle"), it is 0.2 0.6 1.0 1.4 1.8 2.2 suggested that systemic arterial compliance ml/mmHg/m� is higher for those for whom the amount Systemic arterial compliance of physical activity is larger (Figure 3, in submitting). In Figure 3, the relationship between physical activity volume and Figure 2 The relationship between systemic arterial compliance and aerobic exercise capacity systemic arterial compliance is shown by a logarithm regression curve, as the effect of physical activity volume seems to be (ml/mmHg) nonlinear and has an upper threshold. That is, although systemic arterial compliance 3.0 increases linearly when the amount of Systemic arterial compliance physical activity is low, the effect plateaus (age adjusted value) 2.0 when the amount of physical activity exceeds 200-300 kcal per day and appears not to increase any more. The American 1.0 n = 413 College of Sports Medicine (Pate, et al., r = 0.35 1995) recommends a physical activity level p<0.0001 of 200 kcal per day in order to improve 0 physical fitness and to prevent disease. In 0 200 400 600 800 1000 the studies of Paffenbarger, et al. (1978, (kcal/day) Daily physical activity 1986), it was indicated that although people with a physical activity level of more than Figure 3 The relationship between systemic arterial compliance and daily physical activity 2000 kcal per week live longer than those whose level was under 500 kcal per week, the heart attack occurrence rate is the lowest a causal correlation. However, it is known that for those with a physical activity level of 2000-3000 arterial distensibility increases through aerobic kcal per week. It was also indicated that the rate of exercise training, according to some longitudinal risk becomes rather higher when the physical activity studies (Cameron and Dart, 1994, Tanaka, et al, level is more than 4000 kcal per week. Therefore, it 2000, Kakiyama, et al., 2001, Ohtsuki, et al., 2003, is not necessarily true that more physical activity will Kakiyama, et al., 2005). In contrast, carotid artery lead to health benefits. Aerobic exercise of around distensibility decreases in people who continue 200-300 kcal per day is enough for middle-aged and high-resistance training (Miyachi, et al., 2003) and is elderly people. Even if they do more than that, an reported to decrease due to high-resistance training effect matching the amount of increase cannot be (Miyachi, et al., 2004). expected. In our examination using multivariate analysis Exercise intensity (energy consumption per unit with arterial distensibility, age, daily physical activity of time) can influence the effects of exercise, as well level, or risk factors for arteriosclerosis including as total energy consumption. It has been elucidated hyperlipemia as variables (Kakiyama, et al., 1998b, that aerobic exercise training with above moderate International Journal of Sport and Health Science Vol.4, 316-324, 2006 319 http://www.soc.nii.ac.jp/jspe3/index.htm Matsuda, M. p < 0.05 24 ml/mmHg 60 - 69 yrs (n= 9) ● pre-training ○ post-training Systemic arterial compliance 2.0 70 - 77 yrs (n= 7) 20 ◆ pre-training ◇ post-training VO2VT (ml / kg/min) 16 1.0 12 mean ±SD Aerobic exercise capacity: p < 0.05 Systemic arterial compliance: p < 0.05 mean + SD 8 0 0.2 0.6 1.0 1.4 < 30 min 30 min ≦ n=69 n=166 Systemic arterial compliance (ml / mmHg/m2) Moderate-intensity physical activity time Figure 4 Effect of moderate-intensity (3-4 METs) physical Figure 5 Effect of aerobic training on systemic arterial activity on systemic arterial compliance in the elderly (65 yrs <) compliance in the elderly intensity increases arterial distensibility (Cameron physical fitness. Thus, it is presumed that exercise and Dart, 1994, Tanaka, et al., 2000). The American for the improvement of health should not necessarily Heart Association suggests exercise of 4-6 METs for be performed at high intensity. 30 minutes per day as moderate intensity exercise In our longitudinal examination, the effect of (Thompson, et al., 2003). The American College comparatively light intensity exercise on arterial of Sports Medicine recommends a similar fi gure distensibility was also acknowledged. Central arterial (exercise of 3-6 METs) as moderate intensity exercise distensibility and aerobic capacity increased and (Pate, et al., 1995). It is desirable for middle-aged systolic blood pressure declined in middle-aged and and elderly people to do effective lower intensity elderly people six months after starting twice-weekly exercise that can be performed safely and easily. sports lessons that involved light intensity aerobic Thus, we defined moderate intensity exercise that training and muscular strength training (Kakiyama, can be performed safely and easily by middle-aged et al., 2001). Moreover, both systemic arterial and elderly people as 3-5 METs and compared the compliance and aerobic capacity (the amount of effects of different durations of low intensity (under oxygen consumption at the ventilatory threshold) 3 METs), moderate intensity and high intensity increased significantly and systolic blood pressure (above 6 METs) exercise on arterial distensibility declined in middle-aged and elderly people who through multivariate analysis by using cross-sectoral performed aerobic exercise (30 minutes per day, 5 data. A significant effect on arterial distensibility times per week) at 80 % of the ventilatory threshold was not observed in lower intensity exercise, while using a bicycle ergometer, 12 weeks after starting the a significant effect was observed in middle intensity exercise (Otsuki, et al., 2003).Thus, it was indicated exercise and it has been suggested that the effect is that aerobic training of light-to-middle intensity independent of the total amount of activity and the improves arterial distensibility and aerobic capacity amount of high intensity activity. A significant effect in a relatively short time. In contrast, significant was observed even during exercise of 3-4 METs alteration was not observed in arterial compliance intensity, particularly in elderly people (Figure 4). and ventilatory threshold in a study targeting elderly Blair, et al. (1989) studied the relationship between people 70 years of age and older (Otsuki, et al., aerobic capacity and death rate and indicated that 2005). Therefore, it is assumed that the effect of there is an upper threshold in the effect of physical exercise on arterial distensibility becomes less with activity on the decline in death rate and that aging. However, as shown in Figure 5 (which covers continuous moderate intensity exercise for about subjects from 60 to 77 years of age collectively), 30 minutes per day is enough to maintain necessary systemic arterial compliance and ventilatory threshold 320 International Journal of Sport and Health Science Vol.4, 316-324, 2006 http://www.soc.nii.ac.jp/jspe3/index.htm Prevention of Arteriosclerosis ml/mmHg Systemic arterial compliance arterial compliance and systolic blood pressure 2.5 returned to the previous level one year later following a decrease in physical activity volume (Figure 6). 2.0 Moreover, arterial distensibility that increased during 1.5 an eight-week aerobic training programme returned to the former level in the fourth week after stopping 1.0 training in an intervention experiment for younger people (Kakiyama, et al., 2005). This means that it is necessary to build up a habit of physical activity or mmHg Systolic blood pressure continue aerobic exercise training in order to maintain 140 the improved arterial distensibility level. The fact that a positive effect on health can be achieved by adopting 120 a more active lifestyle, even after reaching middle or elderly age, has been reported as in the study of 100 Paffenbarger, et al. (1993). 2.4. Presumptive mechanism of effects of aerobic exercise on arterial distensibility kcal / day Daily physical activity 200 The decline in arterial distensibility with aging is considered to be caused by the age-related progress 150 of organic change, including the alteration and decrease in elastic fibers that are the main elastic component of arterial wall media and the increase in 100 collagen fibers (Nichols and O’Rourke, 1998). The Before After 6 mths After 1 yrs decline in aorta distensibility was restrained as the n = 32 Figure 6 Transition of systemic arterial compliance, systolic age-related alteration of elastic fibers was restrained blood pressure, and daily physical activity in the elderly due to exercise in an experiment using young rats (Matsuda, et al., 1988, 1989, 1993). However, the effect of exercise on the alteration of elastic fibers increased in several subjects 70 years of age and older. was not apparent in older rats (Nasaka, et al., 2003) In addition, the cross-sectoral data demonstrates that and for humans that live longer and whose degree systemic arterial compliance improves as the amount of age-related organic change is large there seems to of physical activity increases in very elderly people be less possibility of restoring elastic fibers through (Figure 3). Given this, it is undeniable that exercise exercise training over a comparatively short term, training can have an effect on elderly people over 70 from several months to half a year. As mentioned years of age. It is possible that an absolute exercise above, the increase in arterial distensibility intensity of under 3 METs for a majority of people in disappeared after a short period due to cessation of this study might make the result ambiguous. Studies exercise training in our study of middle-aged/elderly involving higher intensity exercise are expected to be people and young people (Kakiyama, et al., 2005). performed in the future, as well as studies with more Therefore, it is assumed that some different factors, subjects and of prolonged duration. apart from organic changes to the arterial wall, may The effect of exercise on arterial distensibility be related to the effect emerging in the short-term emerges after a short period both in middle-aged/elderly exercise. Smooth muscle in arterial wall media people and younger people but does not last long. controls artery diameter by changing tension, Systemic arterial compliance and systolic blood through contraction and relaxation, and the tension pressure declined in middle-aged and elderly people of smooth muscle also affects the hardness of the who participated in aerobic exercise training twice a arterial wall. Smooth muscle tension is controlled week, with an increase in physical activity volume by autonomic nervous activity and by a vasoactive six months after starting exercise. However, systemic substance (e.g.nitric oxide and endothelin-1) International Journal of Sport and Health Science Vol.4, 316-324, 2006 321 http://www.soc.nii.ac.jp/jspe3/index.htm Matsuda, M. A B p < 0.01 arbitrary unit n.s. arbitrary unit p < 0.01 p < 0.05 0.25 60 p < 0.05 p < 0.05 0.20 eNOS protein eNOS mRNA 40 0.15 0.10 20 0.05 mean + SE mean + SE 0 0 Young Aged Aged Young Aged Aged n=7 n=7 n=7 n=7 n=7 n=7 Sedentary Training Sedentary Training Figure 7 Expression of endothelial nitric oxide synthase (eNOS) mRNA (A) and eNOS protein (B) in the rat aorta produced by endothelial cells. The increase in function improved during 8 weeks of aerobic training sympathetic activity mainly causes contraction of (Tanabe, et al., 2003b). In addition, nitrite/nitrate smooth muscle, while nitric oxide causes it to relax concentration in the blood increased in middle-aged and endothelin-1 to contract. Since endurance and elderly people after 12 weeks of aerobic training exercise training suppress sympathetic nervous (Maeda, et al., 2004) and endothelin-1 concentration system activity at rest (Jennings, et al., 1997), it is in the blood declined (Maeda, et al., 2003). undeniable that there is a possibility for central artery Nitrite/nitrate in the blood returned to the level it sympathetic activity to suppress as well. Exercise had been before training was begun when exercise training is also known to affect arterial endothelial was intermitted (Maeda, et al., 2004). These results function (Walther, et al., 2004) so that it is possible elucidate a part of an exercise effect mechanism and for these functional factors to be involved in the show the basis for improving the effect of exercise on alteration mechanism of arterial wall distensibility the age-related decrease in arterial wall distensibility during short-term exercise. It has been reported that at the same time. It is also undeniable that there are endothelium-dependent or -independent vasodilation possibilities for the stimulus of short-term exercise of the brachial artery increases in middle-aged and to affect cross-links of collagen fibers which are a elderly people who continue aerobic exercise of strong limiting factor of arterial wall distensibility high intensity (Rywik, et al., 1999), and a significant along with elastic fibers (Tanaka, et al., 2000) and to correlation is observed between physical activity increase arterial wall distensibility by promoting the volume and endothelin-dependent vasodilation new formation of elastic fibers rich in elasticity. of the brachial artery in middle-aged and elderly postmenopausal women (McKechie, et al., 2001). In 3. Conclusion an animal experiment, mRNA of nitric oxide synthase and protein expression was observed to advance in Both the results of previous studies and of our aortic tissues due to aerobic exercise training (Delp own study lead to the following conclusion. That is, and Laughlin, 1997). The result of our experiment, in order to prevent further hardening of arteries, to where older rats were made to exercise (Figure 7), decrease the risk of lifestyle related diseases and to indicates age-related decrease in nitric oxide synthane maintain and enhance vital functions in middle-aged function, as nitric oxide synthase gene and protein and elderly people, it is desirable: 1) to increase expression in aortic endothelium was less in older the activity mass (energy consumption) of aerobic rats compared to young rats, while the synthane exercise, aiming for 200-300 kcal per day; 2) to do 322 International Journal of Sport and Health Science Vol.4, 316-324, 2006 http://www.soc.nii.ac.jp/jspe3/index.htm Prevention of Arteriosclerosis more than 30 minutes of middle intensity exercise Kakiyama, T., Sugawara, J., Murakami, H., Maeda, S., Kuno, per day as part of that exercise; and 3) to ensure S., and Matsuda, M (2005). 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