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Физические тренировки и эндотелиальная дисфункция
Физические тренировки и эндотелиальная дисфункция
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Аннотация
Последние эпидемиологические исследования показали, что такая модификация образа жизни, как аэробные тренировки, снижает частоту сердечно-сосудистых осложнений и смертность в общей популяции. Однако остаются малоизученными механизмы, лежащие в основе антиатерогенных и антигипертензивных эффектов физических тренировок. Артериальная гипертензия ассоциируется с нарушением эндотелиальной функции, которое опосредовано снижением биодоступности оксида азота (NO). У животных с моделированной гипертензией и у людей с гипертонической болезнью было показано, что физические нагрузки улучшают функцию эндотелия. Это свидетельствует о том, что эндотелиальная дисфункция при гипертензии обратима. Предполагается, что изменение образа жизни, в том числе физические тренировки, предотвращает сердечно-сосудистые осложнения путем улучшения эндотелиальной функции у пациентов с артериальной гипертензией. Считается, что физические нагрузки увеличивают синтез NO и снижают уровень его инактивации, что приводит к повышению биодоступности NO. В данном обзоре представлены потенциальные механизмы, которые лежат в основе положительного эффекта тренировок на эндотелиальную функцию у пациентов с артериальной гипертензией.
Ключевые слова: физические тренировки, эндотелиальная функция, оксид азота, окислительный стресс, артериальная гипертензия.
Key words: physical training, endothelial function, nitric oxide, oxidative stress, hypertension.
Ключевые слова: физические тренировки, эндотелиальная функция, оксид азота, окислительный стресс, артериальная гипертензия.
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Key words: physical training, endothelial function, nitric oxide, oxidative stress, hypertension.
Полный текст
Список литературы
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2. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med 2002; 136: 493–503.
3. Mora S, Lee IM, Buring JE, Ridker PM. Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women. JAMA 2006; 295: 1412–9.
4. Gayda M, Brun C, Juneau M et al. Long-term cardiac rehabilitation and exercise training programs improve metabolic parameters in metabolic syndrome patients with and without coronary heart disease. Nutr Metab Cardiovasc Dis 2008; 18 (2): 142–51.
5. Tambalis K, Panagiotakos DB, Kavouras SA, Sidossis LS. Responses of blood lipids to aerobic, resistance, and combined aerobic with resistance exercise training: a systematic review of current evidence. Angiology 2009; 60 (5): 614–32.
6. Wang JS. Exercise and thrombogenesis. J Biomed Sci 2006; 13: 753–61.
7. Evrengul H, Seleci D, Tanriverdi H, Kaftan A. The antiarrhythmic effect and clinical consequences of ischemic preconditioning. Coron Artery Dis 2006; 17: 283–8.
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9. McAllister RM, Laughlin MH. Vascular nitric oxide: effects of physical activity, importance for health. Essays Biochem 2006; 42: 119–31.
10. Griffin KL, Woodman CR, Price EM et al. Endothelium-mediated relaxation of porcine collateral-dependent arterioles is improved by exercise training. Circulation 2001; 104 (12): 1393–8.
11. Sessa WC, Pritchard K, Seyedi N et al. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 1994; 74: 349–53.
12. Goto C, Nishioka K, Umemura T et al. Acute moderate-intensity exercise induces vasodilation through an increase in nitric oxide bioavailiability in humans. Am J Hypertens 2007; 20 (8): 825–30.
13. Higashi Y, Sasaki S, Kurisu S et al. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation 1999; 100: 1194–202.
14. Uematsu M, Ohara Y, Navas JP et al. Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 1995; 269: C1371–C1378.
15. Hudlicka O, Brown M, Egginton S. Angiogenesis in skeletal and cardiac muscle. Physiol Rev 1992; 72: 369–417.
16. Lloyd PG, Prior BM, Yang HT, Terjung RL. Angiogenic growth factor expression in rat skeletal muscle in response to exercise training. Am J Physiol Heart Circ Physiol 2003; 284: H1668–H1678.
17. Gavin TP, Robinson CB, Yeager RC et al. Angiogenesis growth factor response to acute systemic exercise in human skeletal muscle. J Appl Physiol 2003; 96: 19–24.
18. Fontana J, Fulton D, Chen Y et al. Domain mapping studies reveal that the M domain of hsp90 serves as a molecular scaffold to regulate Aktdependent phosphorylation of endothelial nitric oxide synthase and NO release. Circ Res 2002; 90: 866–73.
19. Olfert IM, Breen EC, Mathieu-Costello O, Wagner PD. Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia. J Appl Physiol 2001; 91: 1176–84.
20. Lönn ME, Dennis JM, Stocker R. Actions of «antioxidants» in the protection against atherosclerosis. Free Radic Biol Med 2012; 53 (4): 863–84.
21. Davis ME, Cai H, McCann L et al. Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training. Am J Physiol Heart Circ Physiol 2003; 284: H1449–H1453.
22. Matsumoto A, Hirata Y, Momomura S et al. Increased nitric oxide production during exercise. Lancet 1994; 343: 849–50.
23. Rush JW, Turk JR, Laughlin MH. Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium. Am J Physiol Heart Circ Physiol 2003; 284: H1378–H1387.
24. Higashi Y, Sasaki S, Nakagawa K et al. Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 2002; 346: 1954–62.
25. Van Guilder GP, Westby CM, Greiner JJ et al. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exercise. Hypertension 2007; 50 (2): 403–9.
26. Maeda S, Miyauchi T, Kakiyama T et al. Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans. Life Sci 2001; 69: 1005–16.
27. Lavrencic A, Salobir BG, Keber I. Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome. Arterioscler Thromb Vasc Bio 2000; 20: 551–5.
28. Griffin KL, Laughlin MH, Parker JL. Exercise training improves endothelium-mediated vasorelaxation after chronic coronary occlusion. J Appl Physiol 1999; 87: 1948–56.
29. Yen MH, Tang JH, Sheu JR et al. Chronic exercise enhances endothelium-mediated dilation in spontaneously hypertensive rats. Life Sci 1995; 57: 2205–13.
30. Willson JR, Kapoor SC. Contribution of prostaglandins to exercise-induced vasodilation in humans. Am J Physiol 1993; 265: H171–H175.
2. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med 2002; 136: 493–503.
3. Mora S, Lee IM, Buring JE, Ridker PM. Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women. JAMA 2006; 295: 1412–9.
4. Gayda M, Brun C, Juneau M et al. Long-term cardiac rehabilitation and exercise training programs improve metabolic parameters in metabolic syndrome patients with and without coronary heart disease. Nutr Metab Cardiovasc Dis 2008; 18 (2): 142–51.
5. Tambalis K, Panagiotakos DB, Kavouras SA, Sidossis LS. Responses of blood lipids to aerobic, resistance, and combined aerobic with resistance exercise training: a systematic review of current evidence. Angiology 2009; 60 (5): 614–32.
6. Wang JS. Exercise and thrombogenesis. J Biomed Sci 2006; 13: 753–61.
7. Evrengul H, Seleci D, Tanriverdi H, Kaftan A. The antiarrhythmic effect and clinical consequences of ischemic preconditioning. Coron Artery Dis 2006; 17: 283–8.
8. Taylor RS, Brown A, Ebrahim S et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized trials. Am J Med 2004; 116: 682–97.
9. McAllister RM, Laughlin MH. Vascular nitric oxide: effects of physical activity, importance for health. Essays Biochem 2006; 42: 119–31.
10. Griffin KL, Woodman CR, Price EM et al. Endothelium-mediated relaxation of porcine collateral-dependent arterioles is improved by exercise training. Circulation 2001; 104 (12): 1393–8.
11. Sessa WC, Pritchard K, Seyedi N et al. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 1994; 74: 349–53.
12. Goto C, Nishioka K, Umemura T et al. Acute moderate-intensity exercise induces vasodilation through an increase in nitric oxide bioavailiability in humans. Am J Hypertens 2007; 20 (8): 825–30.
13. Higashi Y, Sasaki S, Kurisu S et al. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation 1999; 100: 1194–202.
14. Uematsu M, Ohara Y, Navas JP et al. Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 1995; 269: C1371–C1378.
15. Hudlicka O, Brown M, Egginton S. Angiogenesis in skeletal and cardiac muscle. Physiol Rev 1992; 72: 369–417.
16. Lloyd PG, Prior BM, Yang HT, Terjung RL. Angiogenic growth factor expression in rat skeletal muscle in response to exercise training. Am J Physiol Heart Circ Physiol 2003; 284: H1668–H1678.
17. Gavin TP, Robinson CB, Yeager RC et al. Angiogenesis growth factor response to acute systemic exercise in human skeletal muscle. J Appl Physiol 2003; 96: 19–24.
18. Fontana J, Fulton D, Chen Y et al. Domain mapping studies reveal that the M domain of hsp90 serves as a molecular scaffold to regulate Aktdependent phosphorylation of endothelial nitric oxide synthase and NO release. Circ Res 2002; 90: 866–73.
19. Olfert IM, Breen EC, Mathieu-Costello O, Wagner PD. Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia. J Appl Physiol 2001; 91: 1176–84.
20. Lönn ME, Dennis JM, Stocker R. Actions of «antioxidants» in the protection against atherosclerosis. Free Radic Biol Med 2012; 53 (4): 863–84.
21. Davis ME, Cai H, McCann L et al. Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training. Am J Physiol Heart Circ Physiol 2003; 284: H1449–H1453.
22. Matsumoto A, Hirata Y, Momomura S et al. Increased nitric oxide production during exercise. Lancet 1994; 343: 849–50.
23. Rush JW, Turk JR, Laughlin MH. Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium. Am J Physiol Heart Circ Physiol 2003; 284: H1378–H1387.
24. Higashi Y, Sasaki S, Nakagawa K et al. Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 2002; 346: 1954–62.
25. Van Guilder GP, Westby CM, Greiner JJ et al. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exercise. Hypertension 2007; 50 (2): 403–9.
26. Maeda S, Miyauchi T, Kakiyama T et al. Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans. Life Sci 2001; 69: 1005–16.
27. Lavrencic A, Salobir BG, Keber I. Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome. Arterioscler Thromb Vasc Bio 2000; 20: 551–5.
28. Griffin KL, Laughlin MH, Parker JL. Exercise training improves endothelium-mediated vasorelaxation after chronic coronary occlusion. J Appl Physiol 1999; 87: 1948–56.
29. Yen MH, Tang JH, Sheu JR et al. Chronic exercise enhances endothelium-mediated dilation in spontaneously hypertensive rats. Life Sci 1995; 57: 2205–13.
30. Willson JR, Kapoor SC. Contribution of prostaglandins to exercise-induced vasodilation in humans. Am J Physiol 1993; 265: H171–H175.
2. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med 2002; 136: 493–503.
3. Mora S, Lee IM, Buring JE, Ridker PM. Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women. JAMA 2006; 295: 1412–9.
4. Gayda M, Brun C, Juneau M et al. Long-term cardiac rehabilitation and exercise training programs improve metabolic parameters in metabolic syndrome patients with and without coronary heart disease. Nutr Metab Cardiovasc Dis 2008; 18 (2): 142–51.
5. Tambalis K, Panagiotakos DB, Kavouras SA, Sidossis LS. Responses of blood lipids to aerobic, resistance, and combined aerobic with resistance exercise training: a systematic review of current evidence. Angiology 2009; 60 (5): 614–32.
6. Wang JS. Exercise and thrombogenesis. J Biomed Sci 2006; 13: 753–61.
7. Evrengul H, Seleci D, Tanriverdi H, Kaftan A. The antiarrhythmic effect and clinical consequences of ischemic preconditioning. Coron Artery Dis 2006; 17: 283–8.
8. Taylor RS, Brown A, Ebrahim S et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized trials. Am J Med 2004; 116: 682–97.
9. McAllister RM, Laughlin MH. Vascular nitric oxide: effects of physical activity, importance for health. Essays Biochem 2006; 42: 119–31.
10. Griffin KL, Woodman CR, Price EM et al. Endothelium-mediated relaxation of porcine collateral-dependent arterioles is improved by exercise training. Circulation 2001; 104 (12): 1393–8.
11. Sessa WC, Pritchard K, Seyedi N et al. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 1994; 74: 349–53.
12. Goto C, Nishioka K, Umemura T et al. Acute moderate-intensity exercise induces vasodilation through an increase in nitric oxide bioavailiability in humans. Am J Hypertens 2007; 20 (8): 825–30.
13. Higashi Y, Sasaki S, Kurisu S et al. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation 1999; 100: 1194–202.
14. Uematsu M, Ohara Y, Navas JP et al. Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 1995; 269: C1371–C1378.
15. Hudlicka O, Brown M, Egginton S. Angiogenesis in skeletal and cardiac muscle. Physiol Rev 1992; 72: 369–417.
16. Lloyd PG, Prior BM, Yang HT, Terjung RL. Angiogenic growth factor expression in rat skeletal muscle in response to exercise training. Am J Physiol Heart Circ Physiol 2003; 284: H1668–H1678.
17. Gavin TP, Robinson CB, Yeager RC et al. Angiogenesis growth factor response to acute systemic exercise in human skeletal muscle. J Appl Physiol 2003; 96: 19–24.
18. Fontana J, Fulton D, Chen Y et al. Domain mapping studies reveal that the M domain of hsp90 serves as a molecular scaffold to regulate Aktdependent phosphorylation of endothelial nitric oxide synthase and NO release. Circ Res 2002; 90: 866–73.
19. Olfert IM, Breen EC, Mathieu-Costello O, Wagner PD. Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia. J Appl Physiol 2001; 91: 1176–84.
20. Lönn ME, Dennis JM, Stocker R. Actions of «antioxidants» in the protection against atherosclerosis. Free Radic Biol Med 2012; 53 (4): 863–84.
21. Davis ME, Cai H, McCann L et al. Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training. Am J Physiol Heart Circ Physiol 2003; 284: H1449–H1453.
22. Matsumoto A, Hirata Y, Momomura S et al. Increased nitric oxide production during exercise. Lancet 1994; 343: 849–50.
23. Rush JW, Turk JR, Laughlin MH. Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium. Am J Physiol Heart Circ Physiol 2003; 284: H1378–H1387.
24. Higashi Y, Sasaki S, Nakagawa K et al. Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 2002; 346: 1954–62.
25. Van Guilder GP, Westby CM, Greiner JJ et al. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exercise. Hypertension 2007; 50 (2): 403–9.
26. Maeda S, Miyauchi T, Kakiyama T et al. Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans. Life Sci 2001; 69: 1005–16.
27. Lavrencic A, Salobir BG, Keber I. Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome. Arterioscler Thromb Vasc Bio 2000; 20: 551–5.
28. Griffin KL, Laughlin MH, Parker JL. Exercise training improves endothelium-mediated vasorelaxation after chronic coronary occlusion. J Appl Physiol 1999; 87: 1948–56.
29. Yen MH, Tang JH, Sheu JR et al. Chronic exercise enhances endothelium-mediated dilation in spontaneously hypertensive rats. Life Sci 1995; 57: 2205–13.
30. Willson JR, Kapoor SC. Contribution of prostaglandins to exercise-induced vasodilation in humans. Am J Physiol 1993; 265: H171–H175.
________________________________________________
2. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med 2002; 136: 493–503.
3. Mora S, Lee IM, Buring JE, Ridker PM. Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women. JAMA 2006; 295: 1412–9.
4. Gayda M, Brun C, Juneau M et al. Long-term cardiac rehabilitation and exercise training programs improve metabolic parameters in metabolic syndrome patients with and without coronary heart disease. Nutr Metab Cardiovasc Dis 2008; 18 (2): 142–51.
5. Tambalis K, Panagiotakos DB, Kavouras SA, Sidossis LS. Responses of blood lipids to aerobic, resistance, and combined aerobic with resistance exercise training: a systematic review of current evidence. Angiology 2009; 60 (5): 614–32.
6. Wang JS. Exercise and thrombogenesis. J Biomed Sci 2006; 13: 753–61.
7. Evrengul H, Seleci D, Tanriverdi H, Kaftan A. The antiarrhythmic effect and clinical consequences of ischemic preconditioning. Coron Artery Dis 2006; 17: 283–8.
8. Taylor RS, Brown A, Ebrahim S et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized trials. Am J Med 2004; 116: 682–97.
9. McAllister RM, Laughlin MH. Vascular nitric oxide: effects of physical activity, importance for health. Essays Biochem 2006; 42: 119–31.
10. Griffin KL, Woodman CR, Price EM et al. Endothelium-mediated relaxation of porcine collateral-dependent arterioles is improved by exercise training. Circulation 2001; 104 (12): 1393–8.
11. Sessa WC, Pritchard K, Seyedi N et al. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 1994; 74: 349–53.
12. Goto C, Nishioka K, Umemura T et al. Acute moderate-intensity exercise induces vasodilation through an increase in nitric oxide bioavailiability in humans. Am J Hypertens 2007; 20 (8): 825–30.
13. Higashi Y, Sasaki S, Kurisu S et al. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation 1999; 100: 1194–202.
14. Uematsu M, Ohara Y, Navas JP et al. Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 1995; 269: C1371–C1378.
15. Hudlicka O, Brown M, Egginton S. Angiogenesis in skeletal and cardiac muscle. Physiol Rev 1992; 72: 369–417.
16. Lloyd PG, Prior BM, Yang HT, Terjung RL. Angiogenic growth factor expression in rat skeletal muscle in response to exercise training. Am J Physiol Heart Circ Physiol 2003; 284: H1668–H1678.
17. Gavin TP, Robinson CB, Yeager RC et al. Angiogenesis growth factor response to acute systemic exercise in human skeletal muscle. J Appl Physiol 2003; 96: 19–24.
18. Fontana J, Fulton D, Chen Y et al. Domain mapping studies reveal that the M domain of hsp90 serves as a molecular scaffold to regulate Aktdependent phosphorylation of endothelial nitric oxide synthase and NO release. Circ Res 2002; 90: 866–73.
19. Olfert IM, Breen EC, Mathieu-Costello O, Wagner PD. Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia. J Appl Physiol 2001; 91: 1176–84.
20. Lönn ME, Dennis JM, Stocker R. Actions of «antioxidants» in the protection against atherosclerosis. Free Radic Biol Med 2012; 53 (4): 863–84.
21. Davis ME, Cai H, McCann L et al. Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training. Am J Physiol Heart Circ Physiol 2003; 284: H1449–H1453.
22. Matsumoto A, Hirata Y, Momomura S et al. Increased nitric oxide production during exercise. Lancet 1994; 343: 849–50.
23. Rush JW, Turk JR, Laughlin MH. Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium. Am J Physiol Heart Circ Physiol 2003; 284: H1378–H1387.
24. Higashi Y, Sasaki S, Nakagawa K et al. Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 2002; 346: 1954–62.
25. Van Guilder GP, Westby CM, Greiner JJ et al. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exercise. Hypertension 2007; 50 (2): 403–9.
26. Maeda S, Miyauchi T, Kakiyama T et al. Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans. Life Sci 2001; 69: 1005–16.
27. Lavrencic A, Salobir BG, Keber I. Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome. Arterioscler Thromb Vasc Bio 2000; 20: 551–5.
28. Griffin KL, Laughlin MH, Parker JL. Exercise training improves endothelium-mediated vasorelaxation after chronic coronary occlusion. J Appl Physiol 1999; 87: 1948–56.
29. Yen MH, Tang JH, Sheu JR et al. Chronic exercise enhances endothelium-mediated dilation in spontaneously hypertensive rats. Life Sci 1995; 57: 2205–13.
30. Willson JR, Kapoor SC. Contribution of prostaglandins to exercise-induced vasodilation in humans. Am J Physiol 1993; 265: H171–H175.
Авторы
С.А.Помешкина
ФГБУ Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний СО РАМН, Кемерово
рomesa@cardio.kem.ru
Research Institute for Complex Problems of cardiovascular diseases, Kemerovo
рomesa@cardio.kem.ru
ФГБУ Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний СО РАМН, Кемерово
рomesa@cardio.kem.ru
________________________________________________
Research Institute for Complex Problems of cardiovascular diseases, Kemerovo
рomesa@cardio.kem.ru
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