Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.
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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Shear stress is an important activator of NO production in the endothelium.
“One important activator of production of NO in the endothelium is shear stress (43, 163).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [163]
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“Recent experimental studies have demonstrated that continued exercise augmented vasodilation evoked by the endothelium-dependent vasodilator acetylcholine (ACh) in dogs (Sessa et al., 1994) and rats (see references in Table 1).”
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Both physical fitness and acute exercise regulate nitric oxide formation in healthy humans
Jungersten, L., Ambring, A., Wall, B., & Wennmalm, Å. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.82.3.760 · Cited by 252 · see citing works
“This observation confirms previous results from studies in animals and humans (2, 10, 18, 23).”
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Effect of aerobic and resistance exercise training on vascular function in heart failure
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Role of Nitric Oxide in the Pathogenesis of Chronic Pulmonary Hypertension
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“Chronic increases in blood flow associated with elevations in physical activity have been shown to increase endothelium-mediated vasodilation, vascular NO synthase mRNA, and protein expression (11, 13, 37, 42, 48), whereas chronic reductions in blood flow induced by hindlimb unloading (36) have been shown to diminish…”
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“, 2005), exercise (Sessa et al., 1994; Yang et al., 2002) and hypoxia (Le Cras et al.”
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“remodeling does not primarily involve vascular smooth muscle.(33) NO also appears to be of minor importance in regard to the vasorelaxation of small arterioles with diameters <100 lm, because these vessels are primarily regulated by myogenic factors.”
BackgroundArterial Mechanical Changes in Children With Familial Hypercholesterolemia
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Exercise Training in Coronary Artery Disease and Coronary Vasomotion
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Self-citationMechanical loading regulates NOS expression and activity in developing and adult skeletal muscle
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Coronary Microcirculation in Health and Disease
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Functional Analysis of the Human Endothelial Nitric Oxide Synthase Promoter
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Self-citationPhysiological mechanisms regulating the expression of endothelial-type NO synthase
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- Authors
- Sessa, W. C., Pritchard, K., Seyedi, N., Wang, J., & Hintze, T. H.
- Affiliations
- New York Medical College (US)
- Venue
- Circulation Research
- Published
- 1994-02
- Volume
- 74
- Issue
- 2
- Pages
- 349-353
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- 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 › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Complementary and alternative medicine › 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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