Abstract
Lifestyle modification is recommended as a non-pharmacological approach to treatment of hypertension. Many investigators have reported that exercise has antihypertensive effects, and various mechanisms have been proposed to explain this phenomenon. For example, nitric oxide (NO), which may be increased by exercise, has been reported to play a crucial role in preserving vessel homeostasis both by regulating vascular tone and by exerting anti-atherosclerotic effects. NO is known to be exquisitely sensitive to inactivation by superoxide radicals. However, the relationship between the blood pressure-lowering effect of lifestyle modification and NO bioavailability remains unknown. We investigated the effects of a 12-week lifestyle modification program consisting of mild exercise and diet on changes in blood pressure, plasma nitrate/nitrite (NOx), plasma nitrotyrosine, which is the footprint of NO interaction with reactive oxygen species, and plasma extracellular-superoxide dismutase (EC-SOD). The 12-week lifestyle modification program lowered blood pressure and increased plasma NOx. When the subjects were divided into two groups according to the change of plasma nitrotyrosine as an indicator of NO bioavailability, the subjects whose plasma nitrotyrosine decreased exhibited a significant relationship between the blood pressure-lowering effect of the lifestyle modification and the increase in EC-SOD, whereas those without a decrease in plasma nitrotyrosine exhibited a significant relationship between the blood pressure-lowering effect and the increase in maximum oxygen consumption. These results indicate that the level of NO bioavailability influences the mechanism of the blood pressure-lowering effect of aerobic exercise and diet.
Similar content being viewed by others
Article PDF
References
Cai H, Harrison DG : Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000; 87: 840–844.
Tomiyama H, Kushiro T, Okazaki R, Yoshida H, Doba N, Yamashina A : Influences of increased oxidative stress on endothelial function, platelets function, and fibrinolysis in hypertension associated with glucose intolerance. Hypertens Res 2003; 26: 295–300.
Kawano H, Motoyama T, Hirai N, Kugiyama K, Yasue H, Ogawa H : Endothelial dysfunction in hypercholesterolemia is improved by L-arginine administration: possible role of oxidative stress. Atherosclerosis 2002; 161: 375–380.
Perticone F, Ceravolo R, Candigliota M, et al: Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C. Diabetes 2001; 50: 159–165.
Ohta M, Nanri H, Omae T, Ikeda M : The effect of lifestyle modification on oxidative stress in obese and non-obese subjects. J UOEH 2002; 24 ( Suppl 2): 99–105.
Oury TD, Day BJ, Crapo JD : Extracellular superoxide dismutase in vessels and airways of humans and baboons. Free Radic Biol Med 1996; 20: 957–965.
Hatori N, Sjoquist PO, Marklund SL, Ryden L : Effects of recombinant human extracellular-superoxide dismutase type C on myocardial infarct size in pigs. Free Radic Biol Med 1992; 13: 221–230.
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure : The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997; 157: 2413–2446.
Guidelines Subcommittee : 1999 World Health Organization–International Society of Hypertension guidelines for the management of hypertension. J Hypertens 1999; 17: 151–183.
Himeno E, Nishino K, Okazaki T, Nanri H, Ikeda M : A weight reduction and weight maintenance program with long-lasting improvement in left ventricular mass and blood pressure. Am J Hypertens 1999; 12: 682–690.
Okazaki T, Himeno E, Nanri H, Ikeda M : Effects of a community-based lifestyle-modification program on cardiovascular risk factors in middle-aged women. Hypertens Res 2001; 24: 647–653.
Ji LL : Exercise-induced modulation of antioxidant defense. Ann N Y Acad Sci 2002; 959: 82–92.
Paffenbarger RS Jr, Hyde RT, Wing AL, Lee IM, Jung DL, Kampert JB : The association of changes in physical activity level and other lifestyle characteristics with mortality among men. N Engl J Med 1993; 328: 538–545.
Blair SN, Kohl HW 3rd, Barlow CE, Paffenbarger RS Jr, Gibbons LW, Macera CA : Changes in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy men. JAMA 1995; 273: 1093–1098.
Ohno H, Suzuki K, Fujii J, et al: Superoxide dismutases in exercise and disease, in Sen CK, Packer L, Häninen O ( eds): Exercise and Oxygen Toxicity. Amsterdam, Elsevier, 1994, pp 127–161.
Fukai T, Siegfried MR, Ushio-Fukai M, Cheng Y, Kojda G, Harrison DG : Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. J Clin Invest 2000; 105: 1631–1639.
Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A : Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation 1998; 97: 2222–2229.
Moriguchi J, Itoh H, Harada S, et al: Low frequency regular exercise improves flow-mediated dilatation of subjects with mild hypertension. Hypertens Res 2005; 28: 315–321.
Taddei S, Galetta F, Virdis A, et al: Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation 2000; 101: 2896–2901.
Green DJ, Maiorana A, O'Driscoll G, Taylor R : Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol 2004; 561: 1–25.
Beckman JS, Koppenol WH : Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996; 271: C1424–C1437.
Halliwell B : What nitrates tyrosine? Is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo? FEBS Lett 1997; 411: 157–160.
Eiserich JP, Butler J, van der Vliet A, Cross CE, Halliwell B : Nitric oxide rapidly scavenges tyrosine and tryptophan radicals. Biochem J 1995; 310: 745–749.
Barton CH, Ni Z, Vaziri ND : Enhanced nitric oxide inactivation in aortic coarctation-induced hypertension. Kidney Int 2001; 60: 1083–1087.
Oury TD, Day BJ, Crapo JD : Extracellular superoxide dismutase: a regulator of nitric oxide bioavailability. Lab Invest 1996; 75: 617–636.
Yagi K : A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 1976; 15: 212–216.
Sato Y, Nanri H, Ohta M, Kasai H, Ikeda M : Increase of human MTH1 and decrease of 8-hydroxydeoxyguanosine in leukocyte DNA by acute and chronic exercise in healthy male subjects. Biochem Biophys Res Commun 2003; 305: 333–338.
Tanaka S, Yashiro A, Nakashima Y, Nanri H, Ikeda M, Kuroiwa A : Plasma nitrite/nitrate is inversely correlated with plasma low-density lipoprotein cholesterol level. Clin Cardiol 1997; 20: 361–365.
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR : Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 1982; 126: 131–138.
Araki M, Nanri H, Ejima K, et al: Antioxidant function of the mitochondrial protein SP-22 in the cardiovascular system. J Biol Chem 1999; 274: 2271–2278.
Hjalmarsson K, Marklund SL, Engstrom A, Edlund T : Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase. Proc Natl Acad Sci U S A 1987; 84: 6340–6344.
Arakawa K : Effect of exercise on hypertension and associated complications. Hypertens Res 1996; 19 ( Suppl 1): S87–S91.
Johnson LR, Parker JL, Laughlin MH : Chronic exercise training improves ACh-induced vasorelaxation in pulmonary arteries of pigs. J Appl Physiol 2000; 88: 443–451.
Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH : Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 1994; 74: 349–353.
Maeda S, Tanabe T, Otsuki T, et al: Moderate regular exercise increases basal production of nitric oxide in elderly women. Hypertens Res 2004; 27: 947–953.
Powers SK, Criswell D, Lawler J, et al: Influence of exercise and fiber type on antioxidant enzyme activity in rat skeletal muscle. Am J Physiol 1994; 266: R375–R380.
Suzuki K, Ohno H, Oh-ishi S, et al: Superoxide dismutases in exercise and disease, in Sen CK, Packer L, Häninen O ( eds): Handbook of Oxidants and Antioxidants in Exercise. Amsterdam, Elsevier, 2000, pp 243–295.
Jonsson LM, Rees DD, Edlund T, Marklund SL : Nitric oxide and blood pressure in mice lacking extracellular-superoxide dismutase. Free Radic Res 2002; 36: 755–758.
Hornig B, Landmesser U, Kohler C, et al: Comparative effect of ACE inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: role of superoxide dismutase. Circulation 2001; 103: 799–805.
Garcia CE, Kilcoyne CM, Cardillo C, Cannon RO 3rd, Quyyumi AA, Panza JA : Effect of copper-zinc superoxide dismutase on endothelium-dependent vasodilation in patients with essential hypertension. Hypertension 1995; 26: 863–868.
Taddei S, Virdis A, Ghiadoni L, et al: Age-related reduction of NO availability and oxidative stress in humans. Hypertension 2001; 38: 274–279.
Adachi T, Weisbrod RM, Pimentel DR, et al: S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide. Nat Med 2004; 10: 1200–1207.
Blair SN, Goodyear NN, Gibbons LW, Cooper KH : Physical fitness and incidence of hypertension in healthy normotensive men and women. JAMA 1984; 252: 487–490.
Kiyonaga A, Arakawa K, Tanaka H, Shindo M : Blood pressure and hormonal responses to aerobic exercise. Hypertension 1985; 7: 125–131.
Minami M, Atarashi K, Ishiyama A, Hirata Y, Goto A, Omata M : Effects of cholesterol-lowering therapy on pressor hyperreactivity to stress in hypercholesterolemic patients. Hypertens Res 2003; 26: 273–280.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ohta, M., Nanri, H., Matsushima, Y. et al. Blood Pressure-Lowering Effects of Lifestyle Modification: Possible Involvement of Nitric Oxide Bioavailability. Hypertens Res 28, 779–786 (2005). https://doi.org/10.1291/hypres.28.779
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.28.779