Cited by 937Nitric Oxide and Endothelin EffectsCardiovascular and exercise physiologyCardiovascular Health and Disease Prevention

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Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.

Sessa, W C, Pritchard, K, Seyedi, N, Wang, J, Hintze, T H·1994·Circulation Research

DOI 10.1161/01.res.74.2.349

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Abstract

Recently, we have shown that chronic exercise increases endothelium-derived relaxing factor (EDRF)/nitric oxide (NO)-mediated epicardial coronary artery dilation in response to brief occlusion and acetylcholine. This finding suggests that exercise can provide a stimulus for the enhanced production of EDRF/NO, thus possibly contributing to the beneficial effects of exercise on the cardiovascular system. Therefore, the purpose of the present study was to examine whether chronic exercise could influence the production of NO (measured as the stable degradation product, nitrite) and endothelial cell NO synthase (ECNOS) gene expression in vessels from dogs after chronic exercise. To this end, dogs were exercised by running on a treadmill (9.5 km/h for 1 hour, twice daily) for 10 days, and nitrite production in large coronary vessels and microvessels and ECNOS gene expression in aortic endothelial extracts were assessed. Acetylcholine (10(-7) to 10(-5) mol/L) dose-dependently increased the release of nitrite (inhibited by nitro-L-arginine) from coronary arteries and microvessels in control and exercised dogs. Moreover, acetylcholine-stimulated nitrite production was markedly enhanced in large coronary arteries and microvessels prepared from hearts of dogs after chronic exercise compared with hearts from control dogs. One potential mechanism that may contribute to the enhanced production of nitrite in vessels from exercised dogs may be the induction of the calcium-dependent ECNOS gene. Steady-state mRNA levels for ECNOS were significantly higher than mRNA levels for von Willebrand's factor (vWF, a specific endothelial cell marker) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a constitutively expressed gene) in exercised dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

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Schöder, H. M., Silverman, D. H. S., Campisi, R., Sayre, J. W., Phelps, M. E., Schelbert, H. R., & Czernin, J. G. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.278.2.h360 · Cited by 32
“In addition, chronic exercise can increase coronary endothelial NO production (38).”
Background
Effects of exercise training on expression of endothelin-1 mRNA in the aorta of aged rats
Maeda, S., Miyauchi, T., Iemitsu, M., et al. (2002) · Clinical Science · doi:10.1042/cs103s118s · Cited by 30
Effect of 1‐week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits
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“…may relate to the altered endothelial function, since a prolonged reduction in peripheral blood ¯ow must lessen shear stress and may lead to a decrease in endothelial NO production and NOS expression in view of previous observations (Miller et al., 1986; Wang et al., 1993; Sessa et al., 1994).”
Result
Chronic Exercise Improves Endothelial Calcium Signaling and Vasodilatation in Hypercholesterolemic Rabbit Femoral Artery
Jen, C. J., Chan, H.-P., & Chen, H. (2002) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000021955.23461.cd · Cited by 30
Influence of Intensive Physical Training on Urinary Nitrate Elimination and Plasma Endothelin-1 Levels in Patients With Congestive Heart Failure
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Physical fitness and endothelial function (nitric oxide synthesis) are independent determinants of insulin-stimulated blood flow in normal subjects
Utriainen, T., Mäkimattila, S., Virkamäki, A., Lindholm, H. J., Sovijärvi, A. R. A., & Yki-Järvinen, H. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.12.8954024 · Cited by 30
“Regarding physical training and endothelial function, in zifro studies in isolated vessel segments and those performed in animals in viva suggested that exercise training might enhance NO synthesis and endothelium-dependent vasodilatory responses to pharmacological stimuli (11-13).”
Background
Determinants of Endothelium-Dependent Femoral Artery Vasodilation in Youth
Treiber, F. A., Papavassiliou, D. P., Gutin, B., Malpass, D., Wang, Y., Islam, S., Davis, H., & Strong, W. B. (1997) · Psychosomatic Medicine · doi:10.1097/00006842-199707000-00007 · Cited by 30
Long-Term Callisthenic Exercise-Related Changes in Blood Lipids, Homocysteine, Nitric Oxide Levels and Body Composition in Middle-Aged Healthy Sedentary Women
Güzel, N. A. (2012) · The Chinese Journal of Physiology · doi:10.4077/cjp.2012.amm122 · Cited by 29
Effect of myostatin deletion on cardiac and microvascular function
Butcher, J. T., Ali, M. I., Merry, W., McCarthy, C. G., Islam, B. N., Fox, L. G., MINTZ, J. D., Larion, S., Fulton, D. J., & Stepp, D. W. (2017) · Physiological Reports · doi:10.14814/phy2.13525 · Cited by 29
“Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society oxide-dependent manner (Wang et al. 1993; Sessa et al. 1994; Koller et al. 1995).”
Background
Effectiveness of melatonin to restore fish brain activity in face of permethrin induced toxicity
Moniruzzaman, M., Mukherjee, M., Das, D., & Chakraborty, S. B. (2020) · Environmental Pollution · doi:10.1016/j.envpol.2020.115230 · Cited by 28
Peripheral Circulation
Laughlin, M. H., Davis, M. J., Secher, N. H., LIESHOUT, J. J. V., Arce‐Esquivel, A. A., Simmons, G. H., Bender, S. B., Padilla, J., Bache, R. J., Merkus, D., et al. (2012) · Comprehensive physiology · doi:10.1002/j.2040-4603.2012.tb00398.x · Cited by 28
Effects of Physical Activity
Wolfram, S. (2006) · Kluwer Academic Publishers eBooks · doi:10.1007/1-4020-8126-x_14 · Cited by 29
Exercise Rescues Gene Pathways Involved in Vascular Expansion and Promotes Functional Angiogenesis in Subcutaneous White Adipose Tissue
Min, S. Y., Learnard, H., Kant, S., Gealikman, O., Rojas-Rodriguez, R., DeSouza, T., Desai, A., Keaney, J. F., Corvera, S., & Craige, S. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20082046 · Cited by 29
“For example, consistent exercise improves vascular function in large conduit vessels such as the aorta, largely through increased expression and activity of eNOS [26].”
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Regulation of Nitric Oxide Synthase Expression and Activity
Förstermann, U. (2000) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-57077-3_4 · Cited by 29
Hyperosmolality dilates rat skeletal muscle arterioles: role of endothelial KATP channels and daily exercise
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“(24) also demonstrated that endothelial nitric oxide synthase mRNA is elevated in canine aorta after 1 wk of daily exercise, suggesting that short-term mild exercise can alter endothelial function.”
Background
The effect of aerobic physical training on cardiac autonomic control of rats submitted to ovariectomy
Tezini, G. C. S. V., Silveira, L. C. R., Villa-Clé, P. G., et al. (2009) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e318182d352 · Cited by 28
Nitric Oxide Inhibition Impairs Blood Flow During Exercise in Hearts With a Collateral-Dependent Myocardial Region
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“Recent evidence indicates that chronic elevations of blood flow can increase NOS gene expression (29).”
Background
Relation of Endothelial Function to Cardiovascular Risk in Women With Sedentary Occupations and Without Known Cardiovascular Disease
Lippincott, M. F., Carlow, A., Desai, A., Blum, A., Rodrigo, M. E., Patibandla, S., Zalos, G., Smith, K., Schenke, W. H., Csákó, G., et al. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.03.069 · Cited by 28
Expression of Endothelial Nitric Oxide Synthase in Human Peritoneal Tissue
Arriero, M., Rodríguez-Feo, J. A., Celdrán, Á., de Miguel, L. S., González-Fernández, F., Fortes, J., Reyero, A., Frieyro, O., de la Pinta, J. C., Franco, A., et al. (2000) · Journal of the American Society of Nephrology · doi:10.1681/asn.v11101848 · Cited by 28
Myocardial Contractile Effects of Nitric Oxide
Paulus, W. J., & Bronzwaer, J. G. F. (2002) · Heart Failure Reviews · doi:10.1023/a:1020754232359 · Cited by 28
“Low LV diastolic stiffness, reversible right- and downward displacement of the diastolic LV pressure-volume relation and high LV preload reserve are typical features of athlete’s heart and could be NOmediated because of the documented upregulation of NOS activity and expression following regular physical exercise [73,…”
Background
Impaired regulation of neuronal nitric oxide synthase and heart rate during exercise in mice lacking one nNOS allele
Danson, E., Mankia, K. S., Golding, S., Dawson, T., Everatt, L., Cai, S., Channon, K. M., & Paterson, D. J. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.062299 · Cited by 28
“Exercise has been implicated as an important factor in the up-regulation of both endothelial nitric oxide (NO) synthase (eNOS) (Sessa et al. 1994) and neuronal NOS (nNOS) (Mohan et al.”
BackgroundInfluential
Chronic exercise training improves ACh-induced vasorelaxation in pulmonary arteries of pigs
Johnson, L. R., Parker, J. L., & Laughlin, M. H. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.2.443 · Cited by 28
“Increased blood flow during exercise is thought to result in increased endothelium-mediated dilation in peripheral vascular beds through shear stress-induced changes in gene expression and protein production (6, 24, 30).”
BackgroundResult
Up‐regulation of endothelial nitric oxide synthase expression by cyclic guanosine 3′,5′‐monophosphate
Ravichandran, L. V., & Johns, R. A. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)01134-z · Cited by 28
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“It is noteworthy that exercise training of control animals typically has been linked with increased eNOS mRNA and protein levels in coronary arteries and arterioles [24,37,41], yet our data do not reveal an increase in eNOS protein levels in arteries of the nonoccluded myocardial region.”
Background
Kynurenic acid attenuates pro-inflammatory reactions in lipopolysaccharide-stimulated endothelial cells through the PPARδ/HO-1-dependent pathway
Lee, T., Park, H. S., Jeong, J. H., & Jung, T. W. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2019.110510 · Cited by 28
Myocardial Contractile Effects of Nitric Oxide
Paulus, W. J., & Bronzwaer, J. G. F. (2006) · Kluwer Academic Publishers eBooks · doi:10.1007/1-4020-7960-5_3 · Cited by 27
“Low LV diastolic stiffness, reversible right- and downward displacement of the diastolic LV pressure-volume relation and high LV preload reserve are typical features of athlete’s heart and could be NOmediated because of the documented upregulation of NOS activity and expression following regular physical exercise [73,…”
Background
Differential Expression of Endothelial Nitric Oxide Synthase in Coronary and Cardiac Tissue in Hypoxic Fetal Guinea Pig Hearts
Dong, Y., & Thompson, L. P. (2006) · Journal of the Society for Gynecologic Investigation · doi:10.1016/j.jsgi.2006.06.005 · Cited by 27
Autologous Bone-Marrow Mesenchymal Stem Cell Implantation and Endothelial Function in a Rabbit Ischemic Limb Model
Mikami, S., Nakashima, A., Nakagawa, K., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067739 · Cited by 27
“[29] demonstrated that the increase in shear stress in epicardial coronary arteries enhanced the expression of the vascular eNOS gene, leading to ACh-stimulated NO release.”
Background
Efficacy of Enhanced External Counterpulsation in Patients With Chronic Refractory Angina on Canadian Cardiovascular Society (CCS) Angina Class
Zhang, C., Liu, X., Wang, X., et al. (2015) · Medicine · doi:10.1097/md.0000000000002002 · Cited by 27

Authors: Sessa, W. C., Pritchard, K., Seyedi, N., Wang, J., & Hintze, T. H.
Affiliations: New York Medical College (US)
ORCID: Sessa, W C
Pritchard, K
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1994-02
Volume: 74
Issue: 2
Pages: 349-353
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/01.res.74.2.349
OpenAlex: W2125823894
Cited by: 934
References: 0
Citations by year: 2026: 2 · 2025: 6 · 2024: 11 · 2023: 8 · 2022: 10 · 2021: 14 · 2020: 17 · 2019: 15 · 2018: 11 · 2017: 11 · 2016: 18 · 2015: 29 · 2014: 18 · 2013: 16 · 2012: 27
FWCI: 32.87
Type: journal article
Language: en
Open access: closed
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association
National Heart, Lung, and Blood Institute (P01HL043023, P01 HL 43023)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Keywords: exercise training, nitric oxide, endothelial nitric oxide synthase, coronary arteries, coronary microvessels, nitrite production, endothelium-derived relaxing factor, acetylcholine, von Willebrand factor, aortic endothelial cells, treadmill running, dogs
MeSH terms: Amino Acid Oxidoreductases, Animals, Coronary Vessels, Dogs, Endothelium, Vascular, Physical Exertion, Female, Male, Nitric Oxide, Nitrites, RNA, Time Factors, Gene Expression, Nitric Oxide Synthase

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Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.

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