This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Angelis, K. L. D. Articles by Irigoyen, M. C. Search for Related Content PubMed PubMed Citation Articles by De Angelis, K. L. D. Articles by Irigoyen, M. C.

(Hypertension. 1997;30:767.)
© 1997 American Heart Association, Inc.

Articles

Exercise Training in Aging

Hemodynamic, Metabolic, and Oxidative Stress Evaluations

K. L. D. De Angelis; A. R. Oliveira; A. Werner; P. Bock; A. Belló-Klein; T. G. Fernandes; A. A. Belló; M. C. Irigoyen

From the Laboratory of Cardiovascular Physiology (K.L.D.De A., A.R.O., A.W., P.B., A.B.-K., T.G.F., A.A.B., M.C.I.), Department of Physiology, Basic and Health Science Institute, University of Rio Grande do Sul, Brazil, and BIC CNPq (A.W., P.B.).

Correspondence to Maria Cláudia Irigoyen, MD, PhD, Department of Physiology, Basic and Health Science Institute, University of Rio Grande do Sul, Brazil, Rua Sarmento Leite, 500. Porto Alegre, Rio Grande do Sul 90050-170.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Abstract The effects of exercise training on hemodynamic and metabolic parameters as well as on responses to oxidative stress in aged individuals are controversial. The aim of the present study was to investigate changes in heart hate, mean arterial pressure, vasoreactivity, and plasma levels of insulin and glucose in male aged Wistar rats submitted to exercise training for 11 weeks (1 h/d; 5 d/wk) in a treadmill. The isolated heart was perfused by H₂O₂, and oxidative stress was evaluated using thiobarbituric acid reactive substances. Cardiovascular functions were recorded with a data acquisition system (CODAS, 1 kHz). Trained aged rats were bradycardic as compared with sedentary aged rats (298±7 versus 336±16 bpm) but presented similar mean arterial pressure and vasoreactivity and plasma levels of insulin and of glucose, which were quantified by radioimmunoassay and colorimetric enzymatic test. Plasma levels of insulin and of glucose ratio were increased in trained aged rats (6.9±0.7 versus 3.5±0.4 in sedentary aged rats), and the response to oxidative stress was decreased (0.4±0.1 versus 0.7±0,1 nmol/mg protein in sedentary aged rats). These results showed that exercise training produced a lower resting heart rate as well as changes in metabolic and oxidative responses. This suggests a higher myocardium protection of trained than sedentary aged rats.

Key Words: exercise training • aging • arterial pressure • glucose • insulin • oxidative stress

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
The aging process is related to morphological and functional changes in the cardiovascular system, glycemia homeostasis, and autonomic control¹ in humans² and rats.^{3 4} Changes in autonomic mechanisms involved in cardiovascular and AP control in aged animal models include reduced cardiac-vagal baroreflex control^{3 5} and increased peripheral sympathetic activity.¹ These changes seem to be related to higher basal insulin and glucose levels^{3 6} or could even be related to other cellular oxygen-metabolizing reactions.⁷ Indeed, there is an increase in the resistance of peripheral tissues to insulin with age⁸ as well as a decreased capacity for physical work.⁹ Studies on young subjects who are obese, glucose intolerant, or non–insulin-dependent diabetic have demonstrated improved peripheral insulin action associated with training programs that increase aerobic capacity.¹⁰ Caloric restriction increases muscle antioxidant capacity in aged animals,⁷ and exercise may induce an increase in antioxidant enzymes activity after 12 weeks of exercise in rats.¹¹ However, there are data suggesting an increase in oxidative stress because of the increase in respiration associated with physical activity.¹² Moreover, exercise induces increased lipid peroxidation¹³ associated with a large increase in free radical concentrations,¹² reinforcing the idea that exercise may increase the rate of aging.¹⁴ The purpose of the present study was to investigate hemodynamic and metabolic changes induced by exercise training in aged rats and the response of the isolated heart to oxidative stress induced by H₂O₂.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Animal Care and Training Program
Fourteen male aged Wistar rats (Animal Quarter House of the Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil), 390±25 g body wt, were fed standard laboratory chow and water ad libitum and housed (4 per cage) in a temperature-controlled room (22°C) with a 12-h dark-light cycle. They were randomly assigned to one of two groups: sedentary (n=7) or trained (n=7).

The exercise training was performed on a treadmill, 5 days per week for 11 weeks, gradually progressing to a speed of 0.9 mph (or 1.45 km/h) at 10% grade for 60 minutes, as described in detail elsewhere.¹⁵

Cardiovascular Evaluations
After the last training session, two catheters filled with 0.06 mL saline were implanted under ether anesthesia into the femoral artery (PE-10) and vein (PE-50) for direct measurements of AP and for drug administration, respectively. Rats fed and watered ad libitum were studied 1 day after catheter placement; the rats were conscious and allowed to move freely during the experiments. The arterial cannula was connected to a strain-gauge transducer (Narco Bio-Systems Miniature Pressure Transducer RP 1500), and blood pressure signals were recorded during a 40-minute period by a microcomputer equipped with an analog-to-digital converter board (CODAS, 1-kHz sampling frequency, Dataq Instruments, Inc). The recorded data were analyzed on a beat-to-beat basis to quantify changes in mean AP and HR. Increasing doses of phenylephrine (0.5 to 2. µg/mL) and sodium nitroprusside (5 to 20 µg/mL) were given as sequential bolus injections (0.1 mL) to produce at least four pressure responses ranging from 5 to 40 mm Hg, as described in detail elsewhere.¹⁶ A time interval between doses was necessary for the blood pressure to return to baseline. Peak increases in MAP after phenylephrine or sodium nitroprusside injection and the corresponding peak reflex changes in HR were recorded for each dose of the drug. Baroreflex sensitivity was evaluated by calculation of the ratio of HR changes to MAP increases or decreases (0 to 10, 11 to 20, 21 to 30, or 31 to 40 mm Hg).

Both vagal effect and IHR were studied¹⁷ by injections of methylatropine (3 mg/kg IV, Sigma) and propranolol (4 mg/kg IV, Sigma) at a maximal volume per injection of 0.2 mL.¹⁷ Resting HR was recorded in a quiet unrestrained rat kept in its own cage. Immediately after the resting HR was recorded, methylatropine was injected. Because the HR response to methylatropine reaches its peak in 10 to 15 minutes,¹⁷ this time interval was standardized before the HR measurement. Propranolol was injected 15 minutes after methylatropine injection, and again the response was measured after 10 to 15 minutes. The IHR was evaluated after simultaneous blockade by propranolol and methylatropine. The vagal effect was evaluated as the difference between the maximum HR after the methylatropine injection and the control HR.

Metabolic Evaluations
Body weight was monitored each week during the period of physical activity. Collection of blood samples was performed at rest in fed rats, before and immediately after the last exercise training session, which occurred 10 weeks after the start of the protocol in the trained group. Blood samples in sedentary rats were collected at rest, with the rats in the fasted state (6 to 8 hours). Plasma glucose and plasma insulin were measured by a colorimetric enzymatic test (Enz color, Bio Diagnostica) and by radioimmunoassay (Pharmacia), respectively.

Oxidative Stress Evaluations
After hemodynamic measurements, animals were killed by a blow to the head, and their chests were opened. The heart was carefully dissected from its connections, and the aorta was retroperfused (Langendorff method) with Tyrode’s solution of the following composition (in mmol/L): 120 NaCl, 5.4 KCl, 1.8 MgCl, 1.25 CaCl₂, 27 NaHCO₃, 2.0 NaH₂PO₄, 1.8 NaSO₄, and 11.1 glucose (pH 7.4). This solution was maintained at 31°C, gassed with O₂/CO₂ (95%/5%), and used for perfusion at constant flow (20 mL/min). The oxidative stress was induced by perfusing the heart with Tyrode’s plus H₂O₂ (1 mmol/L). At the end of perfusion, the heart was homogenized in a ultra-Turrax using 1 g of tissue for 5 mL of 150 mmol/L potassium chloride and 20 mmol/L phosphate buffer (pH 7.4). The protein of the homogenate was assayed by the method of Lowry et al.¹⁸ The suspension was added to thiobarbituric acid and butanol, and aliquots of this homogenate were used for malonaldehyde determination according to the technique of Buege and Aust¹⁹ for TBARS.

Data Analysis
Data are reported as mean±SEM, and Student’s unpaired t test was used to compare values obtained between groups. Correlational studies were evaluated by linear regression analysis.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Hemodynamic Measurements
There were no significant differences in the baseline values between trained and sedentary aged rats for MAP, while resting HR was significantly reduced by 11% in the trained group (Fig 1). Exercise training did not change baroreflex sensitivity in old rats. The heart rate responses for both increases and decreases in AP were similar in trained and sedentary groups. Vagal effect and IHR were not different in either group of aged rats (Table 1).

View larger version (73K): [in this window] [in a new window]   Figure 1. Tracings show resting HR and resting pulse pressure in sedentary aged rats (left) and trained aged rats (right). Note the resting bradycardia in aged trained rats as demonstrated by greater pulse interval.

View this table: [in this window] [in a new window]   Table 1. Hemodynamic Measurements in Trained and Sedentary Aged Rats

Metabolic Measurements
The plasma glucose concentrations measured in the resting state were lower in sedentary (6±0.3 mmol/L) than in trained rats (8±0.2 mmol/L). The exercise training session induced no changes in glycemia of trained aged rats. On the other hand, plasma insulin values at rest were higher in sedentary (199±21 pmol/L) than in trained (121±36 pmol/L) rats. However, exercise training increases plasma glucose values (from 121±36 to 199±28 pmol/L) in trained rats as quantified before and after a training session. The G/I ratio evaluated in resting state was higher in trained (6.9±0.7) than in sedentary aged rats (3.5±0.4). Immediately after exercise training, the G/I ratio decreased in trained rats (4.5±0.6) (Fig 2). The trained group presented decreased body weight as compared with the sedentary one (372±7 versus 422±10 g).

View larger version (29K): [in this window] [in a new window]   Figure 2. G/I ratio at rest in sedentary and trained aged rats as well as in trained rats after a bout of exercise. Values are mean±SEM of 8 subjects. *P<.05 vs sedentary. #P<.05 vs trained rats at rest.

Biochemical Response of H₂O₂-Induced Oxidative Stress
Homogenates of H₂O₂-perfused hearts to evaluate "in vitro" lipoperoxidation showed lower TBARS in the trained (0.4±0.1 nmol/mg protein) than in sedentary aged rats (0.7±0.1 nmol/mg protein). A positive correlation evaluated by linear regression was found between resting HR and basal values of TBARS, showing higher TBARS levels at higher HRs (r=.7, P<.04) (Fig 3).

View larger version (10K): [in this window] [in a new window]   Figure 3. Graph showing positive correlation between resting HR (bpm) and oxidative stress as evaluated by TBARS (nmol/mg protein) expressed by regression line (r=.7, P<.04) in sedentary and trained aged rats.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The main findings of the present study were that exercise training in aged rats is associated with (1) normal AP values and baroreflex sensitivity, (2) reduced resting HR, (3) alterations in insulin sensitivity, and (4) reduced response to H₂O₂-induced oxidative stress.

In the present experiments, a 1-hour recording of AP pulses in conscious rats showed no differences between aged and aged trained rats, confirming data that showed that dynamic exercise training did not modify resting arterial blood pressure of normotensive rats.^{4 20} Although population studies in the Western societies have shown an age-related increase in systolic and diastolic blood pressures,²¹ there has been at least one report in which little or no age-related increases of blood pressure was found²² In rats, we have demonstrated previously³ no change in AP levels of aged rats from the same strain and at the same age as rats used in the present work (18 to 24 months old). Although there is evidence that exercise training decreases resting blood pressure in borderline hypertensive human males and spontaneously hypertensive rats,²³ longitudinal studies have not demonstrated consistent lowering of pressure in either normotensive human males²⁴ or normotensive rats.²⁰

In the present experiments baroreflex response to changes in AP did not modify in aged trained as compared with aged sedentary rats. These results are in contrast to those obtained in young rats, since there are reports showing impairment of baroreflex sensitivity-induced by exercise training.^{4 17} Aging per se induces changes in baroreflex control of HR^{3 5 25} and renal sympathetic nerve activity.²⁶ Recently, we demonstrated in untrained rats from the same strain and age of rats as those used in the present experiments (18 to 24 months old) a reduced sympathoexcitatory response of renal sympathetic activity to decreases in MAP (unpublished observations). In contrast, in the heart the impairment of cardiac-vagal neurons appears to be the major determinant of the changes in HR control with age,^{3 5} since aging reduces the tachycardia induced by atropine in humans and animals.⁵ In trained rats the reduction in tachycardia elicited by atropine injection has been interpreted as the training status,²³ and recently vagal impairment was demonstrated in trained rats²⁶ using an aerobic training program similar to that we used in the present experiments.²⁷ How does exercise training significantly decrease vagal function if it is in fact reduced in aged rats? Indeed, atropine injection in the present experiments induced similar tachycardia in aged and aged trained rats, suggesting a similar level of vagal function in both.

Our results confirm that exercise training causes resting bradycardia, even in aging. However, in contrast to other studies,^{28 29} bradycardia cannot be attributed to an increase of the vagal activity. In fact, the vagal effect as evaluated by atropine injection is similar in both aged and aged trained rats. Although the difference between the maximum HR after methylatropine injection and control HR was similar in both groups of rats, the resting HR was lower (11%) in trained than in sedentary rats. This could indicate a withdrawal of sympathetic activity. However, we did not find differences in IHR and in tachycardic response to MAP decreases (not exceeding 40 mm Hg) in either group of aged rats, suggesting similar sympathetic control of HR, at least in the ranges of MAP changes observed in the present experiments. IHR is reduced in old rats as compared with young ones,²¹ and exercise training did not change this reduction while inducing resting bradycardia. Other mechanisms, such as changes in oxidative stress¹¹ and heart hypertrophy,³⁰ could be related to training bradycardia. Indeed, we found a positive correlation between resting HR and TBARS levels, suggesting that metabolic changes in the myocardium could be related to the exercise bradycardia.

Another finding of the present study was the decrease in plasma insulin level observed in trained rats (47%) before the training session as compared with sedentary ones. Moreover, the differences in resting plasma glucose and insulin allowed us to show that the G/I ratio, an index of insulin sensitivity, was higher in trained than sedentary aged rats. It is well known that aging is accompanied by weight gain, insulin resistance, glucose intolerance, and hyperinsulinemia^{1 3} that have been frequently associated with obesity and hypertension.^{1 31} On the other hand, weight loss and physical training^{32 33} have been shown to improve body sensitivity to insulin while lowering blood pressure in obese and diabetic patients.³⁴ Our results demonstrated that exercise training improves glucose homeostasis in aged individuals, since G/I ratio showed an increase in insulin sensitivity. In fact, there are several reports showing that despite lower insulin levels, glucose tolerance remains normal or improves in response to training.^{16 35} An impressive finding in our experiments was the increase in plasma insulin concentration immediately after the training session, without changes in plasma glucose in trained rats. It suggests an increase in insulin resistance in the postexercise period as shown by the G/I ratio. These results agree with a recent work showing time-course exercise–induced changes in plasma insulin action³⁶ and may be related to the increase in plasma catecholamine levels that may suppress insulin-mediated glucose disposal in skeletal muscle.³⁷ The decrease in AP immediately after a bout of exercise³⁸ may be due to the vasodilator effect of insulin because it is well correlated with blood pressure.³⁹

As described above, exercise training brings about adaptative changes in different systems to enhance the energy supply to skeletal and cardiac muscle. Independently of age, it is well known to increase the biogenesis of mitochondria,⁴⁰ a major source of free radicals.⁴¹ The increase in this organelle has prompted the speculation that exercise training renders the muscle more susceptible to lipid peroxidation.⁴² In the present work the myocardial response to oxidative stress induced by H₂O₂ was significantly lower in trained than in sedentary aged rats. H₂O₂ perfused into the aorta of the isolated rat heart induces a positive inotropic effect followed by the depression of contractility or cardiac contractures. The last effect is similar to the "stone heart" observed in reperfusion injury and may be ascribed to lipoperoxidation of the membrane lipid.⁴³ In fact, H₂O₂ perfusion of rat heart increased lipoperoxidation of cardiac homogenates.⁴³ The reduced TBARS level in the heart of trained aged rats, as compared with sedentary ones, suggests an improvement of myocardial protection in the former. Despite the different data showing an increase in oxidative stress^{12 13} induced by exercise, our results showed, at least at the myocardium, a higher resistance to this stress. On the other hand, the finding that there is a positive correlation between resting HR and the values of TBARS may suggest adaptative changes in different systems at the myocardium to minimize the energy cost of the cardiac work.

In summary, exercise training in aged normotensive rats did not modify AP or baroreflex sensitivity. However, exercise training changes metabolic profile and decreases HR, improving myocardial protection to oxidative stress. Moreover, the weight loss observed in trained aged rats may be taken into account as changes not only in insulin sensitivity³² but also in autonomic function, as demonstrated previously in humans.⁴⁴ These changes in aged rats represent an adaptative response to the demands of training to provide a more efficient physiological condition.

	Selected Abbreviations and Acronyms

 

AP = arterial pressure G/I = glucose/insulin HR = heart rate IHR = intrinsic heart rate MAP = mean arterial pressure TBARS = thiobarbituric acid reactive substances

	Acknowledgments

 
This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Finaciadora de Estudos e Projetos (FINEP), Fundação de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and Propesp-UFRGS.

Received March 17, 1997; first decision April 30, 1997; accepted June 2, 1997.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Docherty JR. Cardiovascular responses in aging: a review. Pharmacol Rev. 1990;42:103-125.[Medline] [Order article via Infotrieve]
2. Lipson LG, Bobrycki VA, Buch MJ, Tietjen GE, Yoon A. Insulin release in aging: studies on adenylate cyclase, phosphodiesterase and protein kinase in isolated islets of Langerhans of the rat. Endocrinology. 1982;108:620-624.
3. Werner A, Rosa NRS, Oliveira AR, Fernades TG, Belló AA, Irigoyen MC. Changes in blood pressure control in aged rats. Braz J Med Biol Res. 1995;28:603-607.[Medline] [Order article via Infotrieve]
4. Negrao CE, Irigoyen MC, Moreira ED, Brum PC, Freire PM, Krieger EM. Effect of exercise training on RSNA, baroreflex control, and blood pressure responsiveness. Am J Physiol. 1993;265:R365-R370.[Medline] [Order article via Infotrieve]
5. Ferrari AU, Daffonchio A, Gerosa S, Mancia G. Alterations in cardiac parasympathetic function in aged rats. Am J Physiol. 1991;260:H647-H649.[Medline] [Order article via Infotrieve]
6. Machado UF, Nogueira CR, Carpinelli AR. Obesity is the major cause of alterations in insulin secretion and calcium fluxes by isolated islets from aged rats. Physiol Behav. 1992;52:717-721.[Medline] [Order article via Infotrieve]
7. Starnes JW, Cantu G, Farrar RP, Keher JP. Skeletal muscle lipid peroxidation in exercised and food-restricted rats during aging. J Appl Physiol. 1989;67:69-75.[Abstract/Free Full Text]
8. Fine RI, Kolterman OG, Griffin J, Olefsky JM. Mechanisms of insulin resistance with aging. J Clin Invest. 1983;71:1523-1535.[Medline] [Order article via Infotrieve]
9. Hossack KF, Bruce RA. Maximal cardiac function in sedentary normal men and women: comparison of age-related changes. J Appl Physiol. 1982;53:799-804.[Abstract/Free Full Text]
10. DeFronzo RA, Sherwin RS, Kramer N. Effect of physical training on insulin action in obesity. Diabetes. 1987;36:1379-1385.[Abstract]
11. Jenkins RR. The role of superoxide dismutase and catalase in muscle fatigue. In: Biochemistry of Exercise. Champaign, IL: Human Kinetics; 1983:467-471.
12. Davies KJA, Quintanilha AT, Brooks GA, Packer L. Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun. 1982;107:1198-1205.[Medline] [Order article via Infotrieve]
13. Dillard CJ, Litvov TL, Tappel AL. Effects of dietary vitamin E, selenium, and polyunsaturated fats on in vivo lipid peroxidation J Appl Physiol. 1978;45:927-932.[Abstract/Free Full Text]
14. Sohal RS, Allen RG. Relationship between oxygen metabolism, aging and development. Adv Free Radical Biol Med. 1986;2:117-160.
15. Raad DM, Everett LS, Crenshaw TD, Thomas DP. Bone mechanical properties after exercise training in young and old rats. J Appl Physiol. 1990;68:130-134.[Abstract/Free Full Text]
16. Irigoyen MC, Moreira RD, Moreira ED, Krieger EM. High-renin renal hypertension depresses the baroreflex control of heart rate and sympathetic activity. In: Kunos G, Ciriello J, eds. Central Neural Mechanisms of Blood Pressure Regulation. New York, NY: Springer Verlag; 1991:254-264.
17. Negrão CE, Moreira ED, Santos MCLM, Farah VMA, Krieger EM. Vagal function impairment after exercise training. J Appl Phisyol. 1992;72:1749-1753.
18. Lowry OH, Rosebrough MJ, Farr AL, Randall RJ. Protein measurement with the Folin reagent. J Biol Chem. 1951;193:265.[Free Full Text]
19. Buege JA, Aust SD. Microsomal lipid peroxidation. In: Fleischer S, Packer L, eds. Methods in Enzymology. Orlando, Fla: Academic Press Inc; 1978;52:302-309.
20. Lutgemeier I, Luft FC, Unger T, Ganten U, Lang RE, Gless KH, Ganten D. Blood pressure, electrolyte and adrenal responses in swim-trained hypertensive rats. J Hypertens. 1987;5:241-247.[Medline] [Order article via Infotrieve]
21. Folkow B, Svanborg A. Physiology of cardiovascular aging. Physiol Rev. 1993;73:725-764.[Free Full Text]
22. Friberg P, Nordlander M, Lundin S, Folkow B. Effects of ageing on cardiac performance and coronary flow in spontaneously hypertensive and normotensive rats. Acta Physiol Scand. 1985;125:1-11.[Medline] [Order article via Infotrieve]
23. Tipton CM, Carey RA, Eastin WC, Erickson HH. A submaximal test for dogs: evaluation of effects of training, detraining, and cage confinement. J Appl Physiol. 1974;37:271-275.[Free Full Text]
24. Adragna NC, Cang JL, Morey MC, Williams RS. Effect of exercise on cation transport in human red cells. Hypertension. 1985;7:132-139.[Abstract/Free Full Text]
25. Franchini KG, Moreira ED, Ida F, Krieger EM. Alterations in the cardiovascular control by the chemoreflex and the baroreflex in old rats. Reg Int Comp Physiol. 1996;39:R310-R313.
26. Hajduczok G, Chapleau MW, Jonhson SL, Abboud FM. Increase in sympathetic activity with age, I: role of impairment of arterial baroreflexes. Am J Physiol. 1991;261(Heart Circ Physiol 29):H1113-H11120.
27. Negrão CE, Ji LL, Schaurer JE, Nagle FJ, Lardy HA. Carnitine supplementation and depletion: tissue carnitines and enzymes in fatty acid oxidation. J Appl Physiol. 1987;63:315-321.[Abstract/Free Full Text]
28. Scheuer J, Tipton CM. Cardiovascular adaptations to physical training. Annu Rev Physiol. 1977;101:481-488.
29. Smith ML, Hudson DL, Graitzer HM, Raven PB. Exercise training bradycardia: the role of autonomic balance. Med Sci Sports Exercise. 1989;21:40-44.[Medline] [Order article via Infotrieve]
30. Sigvardsson K, Svanfeldt E, Kilbom A. Role of the adrenergic nervous system in development of training-induced bradycardia. Acta Physiol Scand. 1977;101:481-488.[Medline] [Order article via Infotrieve]
31. Hall JE. Hyperinsulinemimia: a link between obesity and hypertension? Kidney Int. 1993;43:1402-1417.[Medline] [Order article via Infotrieve]
32. Tuck ML, Sowers J, Dornfeld L, Kledzik G, Maxwell M. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med. 1981;304:930-933.[Abstract]
33. Horton ES. The role of exercise in the treatment of hypertension in obesity. Int J Obes. 1981;5(suppl I):165-171.
34. Henry RR, Wallace P, Olefsky JM. Effects of weight loss on mechanisms of hyperglycemia in obese non-insulin-dependent diabetes mellitus. Diabetes. 1986;35:990-998.[Abstract]
35. Heath GW, Gavin III JR, Hinderliter JM, Hagberg JM, Bloomfield SA, Holloszy JO. Effects of exercise and lack of exercise on glucose tolerance and insulin sensitivity. J Appl Physiol. 1983;55:512-517.[Abstract/Free Full Text]
36. King DS, Baldus PJ, Sharp RL, Kesl LD, Feltmeyer TL, Riddle MS. Time course for exercise-induced alterations in insulin action and glucose tolerance in middle-aged people. J Appl Physiol. 1995;78:17-22.[Abstract/Free Full Text]
37. James DE, Burleigh KM, Kraegen EW. In vivo glucose metabolism in individual tissue of the rat. Interaction between epinephrine and insulin. J Biol Chem. 1986;261:6366-6374.[Abstract/Free Full Text]
38. Victor RG, Seals DR, Mark AL. Differential control of heart rate and sympathetic nerve activity during dynamic exercise. J Clin Invest. 1987;79:508-516.[Medline] [Order article via Infotrieve]
39. Feldman RD, Bierbrier GS. Insulin-mediated vasodilation: impairment with increased blood pressure and body mass. Lancet. 1993;342:707-709.[Medline] [Order article via Infotrieve]
40. Cartee GD, Farrar RP. Muscle respiratory capacity and VO₂ max in identically trained young and old rats. J Appl Physiol.. 1987;63:257-261.[Abstract/Free Full Text]
41. Horton AA, Fairhurst S. Lipid peroxidation and mechanisms to toxicity. CRC Crit Rev Toxicol. 1987;18:27-79.[Medline] [Order article via Infotrieve]
42. Gohil K, Rothfuss L, Lang J, Packer L. Effect of exercise training on tissue vitamin E and ubiquinone content. J Appl Physiol. 1987;63:1638-1641.[Abstract/Free Full Text]
43. Belló AA, Bello-Klein A, Oliveira AR, Brunetto AF, Irigoyen MC, Bauerman LF, Miranda MFS, Llesuy S. Hydrogen peroxide as a tool for studying oxidative stress in the heart. J Braz Ass Adv Sci. 1996;48(1/2):27-36.
44. Hirsch J, Leibel RL, Mackintosh R, Aguirre A. Heart rate variability as a measure of autonomic function during weight change in humans. Am J Physiol. 1991;261:R1418-R1423.[Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				S. B.C. Souza, K. Flues, J. Paulini, C. Mostarda, B. Rodrigues, L. E. Souza, M.-C. Irigoyen, and K. De Angelis Role of Exercise Training in Cardiovascular Autonomic Dysfunction and Mortality in Diabetic Ovariectomized Rats Hypertension, October 1, 2007; 50(4): 786 - 791. [Abstract] [Full Text] [PDF]

				M.-C. Irigoyen, J. Paulini, L. J. F. Flores, K. Flues, M. Bertagnolli, E. Dias Moreira, F. Consolim-Colombo, A. Bello-Klein, and K. De Angelis Exercise Training Improves Baroreflex Sensitivity Associated With Oxidative Stress Reduction in Ovariectomized Rats Hypertension, October 1, 2005; 46(4): 998 - 1003. [Abstract] [Full Text] [PDF]

				C. Napoli, S. Williams-Ignarro, F. de Nigris, L. O. Lerman, L. Rossi, C. Guarino, G. Mansueto, F. Di Tuoro, O. Pignalosa, G. De Rosa, et al. Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice PNAS, June 8, 2004; 101(23): 8797 - 8802. [Abstract] [Full Text] [PDF]

				K. De Angelis, R. B. Wichi, W. R. A. Jesus, E. D. Moreira, M. Morris, E. M. Krieger, and M. C. Irigoyen Exercise training changes autonomic cardiovascular balance in mice J Appl Physiol, June 1, 2004; 96(6): 2174 - 2178. [Abstract] [Full Text] [PDF]

				M. Iemitsu, T. Miyauchi, S. Maeda, T. Tanabe, M. Takanashi, Y. Irukayama-Tomobe, S. Sakai, H. Ohmori, M. Matsuda, and I. Yamaguchi Aging-induced decrease in the PPAR-alpha level in hearts is improved by exercise training Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1750 - H1760. [Abstract] [Full Text] [PDF]

				P. Abete, N. Ferrara, F. Cacciatore, E. Sagnelli, M. Manzi, V. Carnovale, C. Calabrese, D. de Santis, G. Testa, G. Longobardi, et al. High level of physical activity preserves the cardioprotective effect of preinfarction angina in elderly patients J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1357 - 1365. [Abstract] [Full Text] [PDF]

				M. C. Irigoyen, E. D. Moreira, A. Werner, F. Ida, M. D. Pires, I. A. Cestari, and E. M. Krieger Aging and baroreflex control of RSNA and heart rate in rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2000; 279(5): R1865 - R1871. [Abstract] [Full Text] [PDF]

				P. Abete, C. Calabrese, N. Ferrara, A. Cioppa, P. Pisanelli, F. Cacciatore, G. Longobardi, C. Napoli, and F. Rengo Exercise training restores ischemic preconditioning in the aging heart J. Am. Coll. Cardiol., August 1, 2000; 36(2): 643 - 650. [Abstract] [Full Text] [PDF]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Angelis, K. L. D. Articles by Irigoyen, M. C. Search for Related Content PubMed PubMed Citation Articles by De Angelis, K. L. D. Articles by Irigoyen, M. C.