Effects of Age and Exercise Training on Nitric Oxide Bioavailability in Cerebral Resistance Arteries

Flow-induced vasodilation is attenuated with old age in rat skeletal muscle arterioles. The purpose of this study was to determine whether diminished cyclooxygenase (COX) signaling contributes to the age-induced attenuation of flow-induced vasodilation in gastrocnemius muscle arterioles and to determine whether, and through which mechanism(s), exercise training restores this deficit in old rats. Fischer 344 rats (3 and 22 mo old) were assigned to a sedentary or exercise-trained group. First-order arterioles were isolated from the gastrocnemius muscles, cannulated, and pressurized to 70 cmH2O. Diameter changes were determined in response to graded increases in intraluminal flow in the presence and absence of nitric oxide synthase (NOS) inhibition [10−5 M NG-nitro-l-arginine methyl ester (l-NAME)], COX inhibition (10−5 M indomethacin), or combination NOS (10−5 Ml-NAME) plus COX (10−5 M indomethacin) inhibition. Aging reduced flow-induced vasodilation in gastrocnemius muscle arterioles. Exercise training restored responsiveness to flow in arterioles of aged rats and enhanced flow-induced vasodilation in arterioles from young rats. l-NAME inhibition of flow-induced vasodilation was greater in arterioles from old rats compared with those from young rats and was increased after exercise training in arterioles from both young and old rats. Although the indomethacin-sensitive portion of flow-induced dilation was not altered by age or training, both COX-1 mRNA expression and PGI2 production increased with training in arterioles from old rats. These data demonstrate that exercise training restores flow-induced vasodilation in gastrocnemius muscle arterioles from old rats and enhances flow-induced vasodilation in gastrocnemius muscle arterioles from young rats. In arterioles from both old and young rats, the exercise training-induced enhancement of flow-induced dilation occurs primarily through a NOS mechanism.

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Effect of exercise training on resistance arteries in rats with chronic NOS inhibition

Journal of Applied Physiology ◽

10.1152/japplphysiol.91180.2008 ◽

2009 ◽

Vol 107 (3) ◽

pp. 896-902 ◽

Cited By ~ 33

Author(s):

Oktay Kuru ◽

Ümit Kemal Şentürk ◽

Günnur Koçer ◽

Sadi Özdem ◽

Oǧuz K. Başkurt ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Exercise Training ◽

Experimental Hypertension ◽

Flow Mediated Dilation ◽

Resistance Arteries ◽

Hypertensive Rats ◽

Inhibition Model ◽

Exercise Effect ◽

Relaxation Responses

Regular exercise has blood pressure-lowering effects, as shown in different types of experimental hypertension models in rats, including the nitric oxide synthase (NOS) inhibition model. We aimed to investigate possible mechanisms implicated in the exercise effect by evaluating the vasoreactivity of resistance arteries. Exercise effects on agonist-induced vasodilatory responses and flow-mediated dilation were evaluated in vessel segments of the rat chronic NOS inhibition model. Normotensive and hypertensive rats were subjected to swimming exercise (1 h/day, 5 days/wk, 6 wk), while rats in other sedentary and hypertensive groups did not. Hypertension was induced by oral administration of the nonselective NOS inhibitor l-NAME (25 mg/kg day) for 6 wk. Systolic blood pressure, as measured by the tail-cuff method, was significantly decreased by the training protocol in exercising hypertensive rats. The vasoreactivity of resistance arteries was evaluated by both wire and pressure myography studies. An impaired nitric oxide-mediated relaxation pathway in untrained hypertensive rats led to decreased relaxation responses in vessels with intact endothelium. Exercise training significantly improved the responses to acetylcholine and flow-mediated dilation in exercise-trained hypertensive rats in parallel with a decrease in blood pressure. On the other hand contraction (norepinephrine and KCl) and relaxation (sodium nitroprusside) responses of vascular smooth muscle were not different between the groups. Vascular endothelial NOS protein expression was found to be increased in both exercising groups. In conclusion, these results revealed evidence of an increased role of the nitric oxide-dependent relaxation pathway in exercising hypertensive rats.

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NOS expression and activity in cerebral resistance arteries: Effects of age and exercise training

The FASEB Journal ◽

10.1096/fasebj.20.4.a812-b ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Amanda Jo LeBlanc ◽

Kathryn Nichol ◽

Christopher R Woodman ◽

Robert D. Shipley ◽

Rhonda D Prisby ◽

...

Keyword(s):

Exercise Training ◽

Resistance Arteries ◽

Cerebral Resistance ◽

Expression And Activity

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Different Responses Of Arterial Stiffness And Nitric Oxide Bioavailability To Different Exercise Training Programs

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000536865.70073.b6 ◽

2018 ◽

Vol 50 (5S) ◽

pp. 540

Author(s):

Natsuki Hasegawa ◽

Shumpei Fujie ◽

Naoki Horii ◽

Eri Miyamoto-Mikami ◽

Katsunori Tsuji ◽

...

Keyword(s):

Nitric Oxide ◽

Exercise Training ◽

Arterial Stiffness ◽

Training Programs ◽

Nitric Oxide Bioavailability

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Vascular Nitric Oxide and Oxidative Stress: Determinants of Endothelial Adaptations to Cardiovascular Disease and to Physical Activity

Canadian Journal of Applied Physiology ◽

10.1139/h05-133 ◽

2005 ◽

Vol 30 (4) ◽

pp. 442-474 ◽

Cited By ~ 75

Author(s):

James W.E. Rush ◽

Steven G. Denniss ◽

Drew A. Graham

Keyword(s):

Oxidative Stress ◽

Physical Activity ◽

Nitric Oxide ◽

Cardiovascular Disease ◽

Endothelial Dysfunction ◽

Exercise Training ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

And Oxidative Stress ◽

Nitric Oxide Bioavailability

Cardiovascular disease is the single leading cause of death and morbidity for Canadians. A universal feature of cardiovascular disease is dysfunction of the vascular endothelium, thus disrupting control of vasodilation, tissue perfusion, hemostasis, and thrombosis. Nitric oxide bioavailability, crucial for maintaining vascular endothelial health and function, depends on the processes controlling synthesis and destruction of nitric oxide as well as on the sensitivity of target tissue to nitric oxide. Evidence supports a major contribution by oxidative stress-induced destruction of nitric oxide to the endothelial dysfunction that accompanies a number of cardiovascular disease states including hypertension, diabetes, chronic heart failure, and atherosclerosis. Regular physical activity (exercise training) reduces cardiovascular disease risk. Numerous studies support the hypothesis that exercise training improves vascular endothelial function, especially when it has been impaired by preexisting risk factors. Evidence is emerging to support a role for improved nitric oxide bioavailability with training as a result of enhanced synthesis and reduced oxidative stress-mediated destruction. Molecular targets sensitive to the exercise training effect include the endothelial nitric oxide synthase and the antioxidant enzyme superoxide dismutase. However, many fundamental details of the cellular and molecular mechanisms linking exercise to altered molecular and functional endothelial phenotypes have yet to be discovered. The working hypothesis is that some of the cellular mechanisms contributing to endothelial dysfunction in cardiovascular disease can be targeted and reversed by signals associated with regular increases in physical activity. The capacity for exercise training to regulate vascular endothelial function, nitric oxide bioavailability, and oxidative stress is an example of how lifestyle can complement medicine and pharmacology in the prevention and management of cardiovascular disease. Key words: exercise, artery, reactive oxygen species, antioxidant, hypertension

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Induction of nitric oxide synthase mRNA in coronary resistance arteries isolated from exercise-trained pigs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.6.h2575 ◽

1997 ◽

Vol 273 (6) ◽

pp. H2575-H2579 ◽

Cited By ~ 61

Author(s):

Christopher R. Woodman ◽

Judy M. Muller ◽

M. Harold Laughlin ◽

Elmer M. Price

Keyword(s):

Gene Expression ◽

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Exercise Training ◽

Mrna Expression ◽

Coronary Resistance ◽

Resistance Arteries ◽

Miniature Swine ◽

Polymerase Chain ◽

Oxide Synthase

The purpose of this study was to develop a method by which endothelial cell nitric oxide synthase (ecNOS) mRNA expression could be measured in single coronary resistance arteries and to test the hypothesis that ecNOS gene expression is upregulated by exercise training. Yucatan miniature swine were randomly assigned to exercise-trained (ET; n = 5) or sedentary (Sed; n = 4) groups for 16 wk. Individual coronary resistance arteries (50–100 μm) were dissected, frozen in liquid nitrogen, and homogenized in a LiCl buffer. mRNA was isolated from each vessel, and ecNOS gene expression was assessed using reverse transcriptase (RT)-polymerase chain reaction (PCR) standardized by coamplifying ecNOS with glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The ecNOS-to-GAPDH amplicon ratio was significantly greater in coronary resistance arteries isolated from ET pigs than in Sed controls. On the basis of these data, it is concluded that RT-PCR can be used on single coronary resistance arteries to assess cell-specific mRNA expression and that ecNOS gene expression is upregulated by exercise training in porcine coronary resistance arteries.

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