Tetrahydrobiopterin augments endothelium‐dependent dilatation in sedentary but not in habitually exercising older adults

Eskurza, Iratxe; Myerburgh, Laura A.; Kahn, Zachary D.; Seals, Douglas R.

doi:10.1113/jphysiol.2005.092734

Cited by 154 publications

(157 citation statements)

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“…Aging is associated with impaired vascular endothelial function [17][18][19]21,36,37 and increased risk of CVD, independent of obesity. 15 As such, interventions that can improve endothelial function in overweight and obese middle-aged and older adults have important clinical implications for preventing age-associated CVD.…”

Section: Discussionmentioning

confidence: 99%

Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults

et al. 2008

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Abstract-Obesity is associated with vascular endothelial dysfunction, as indicated by impaired endothelium-dependent dilation. Presently there is no direct evidence that energy intake-restricted weight loss alone improves conduit or resistance artery endothelium-dependent dilation, the mechanisms involved, or whether improvements differ with patient age. A total of 40 overweight or obese (body mass index: Ն25Ͻ40 kg/m 2 ) nondiabetic men and women aged 21 to 69 years completed 12 weeks of reduced energy intake (nϭ26; 15 male) or attention control (nϭ14; 9 male) and 4 weeks of weight maintenance (randomized trial). Energy intake restriction reduced estimated total energy intake (33%), body weight (10.5%), total and abdominal body fat, plasma leptin, oxidized low-density lipoprotein, and improved several metabolic risk factors. Brachial artery flow-mediated dilation was increased by 30% (6.0Ϯ0.7% versus 7.9Ϯ0.7%⌬; Pϭ0.01; nϭ17). Peak forearm blood flow during intrabrachial artery infusion of acetylcholine was increased by 26% (16.8Ϯ1.4 versus 21.1Ϯ1.9 mL/100 mL per minute; PϽ0.05; nϭ15); this was inversely related to the reduction in the abdominal visceral:subcutaneous fat ratio (rϭϪ0.46; PϽ0.05) and was abolished by inhibition of NO synthesis with N G -monomethyl-L-arginine. Improvements in endothelium-dependent dilation were not related to age: mean increases in subjects Ͼ50 years of age were similar to or greater than those Ͻ50 years of age. Energy intake-restricted weight loss alone is an effective intervention for improving peripheral conduit and resistance artery endothelial function in young and older overweight/obese adults. The improvements in resistance artery function are mediated by an increase in NO bioavailability and are related to reductions in abdominal visceral fat. Key Words: endothelium Ⅲ obesity Ⅲ intra-abdominal fat Ⅲ nitric oxide Ⅲ energy intake Ⅲ adipokines Ⅲ aging O besity is associated with increased risk of cardiovascular diseases (CVDs), believed attributable in part to vascular endothelial dysfunction, as indicated by impaired endothelium-dependent dilation (EDD). 1,2 Thus, interventions that improve EDD in overweight and obese adults may have important clinical implications for the prevention of CVD.As reviewed recently, 3 surgical treatment, short-term verylow calorie diets, and multicomponent lifestyle interventions that include aerobic exercise and weight loss generally lead to improvements in EDD, particularly in overweight/obese adults with comorbidities. However, presently there is no evidence that moderate energy intake restriction-based weight loss alone improves EDD in otherwise healthy overweight/obese adults, 3 and no randomized trial with a nonweight loss control has been conducted on this question. This is important in that many overweight or obese adults who have not yet developed other clinical disorders are not candidates for gastric-bypass surgery, cannot sustain diets involving severe caloric restriction, and/or will not exercise regularly.If energy intake restriction...

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Section: Discussionmentioning

confidence: 99%

Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults

et al. 2008

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“…With the sample size of 20 subjects, the current study had 80% power (alphaϭ0.05) to detect a change of 22% (1.6 percentage points) in flow-mediated dilation and 15% (170 mL/min) in hyperemic flow, which are comparable to the differences between sedentary and active individuals. 27 …”

Section: Discussionmentioning

confidence: 99%

Physical Inactivity Rapidly Induces Insulin Resistance and Microvascular Dysfunction in Healthy Volunteers

Hamburg

McMackin

Huang

et al. 2007

ATVB

376

295

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Objectives-Sedentary lifestyle increases the risk of cardiovascular disease and diabetes. Vascular dysfunction contributes to atherogenesis and has been linked to insulin resistance. Methods and Results-We measured insulin sensitivity by glucose tolerance test and vascular function by ultrasound and venous occlusion plethysmography in 20 healthy subjects (14 men, 6 women) at baseline and during 5 days of bed rest.Bed rest led to a 67% increase in the insulin response to glucose loading (PϽ0.001) suggesting increased insulin resistance and produced increases in total cholesterol and triglycerides. Bed rest led to decreased reactive hyperemia in the forearm (1317Ϯ404 to 1112Ϯ260 mL/min, Pϭ0.01) and the calf (28.5Ϯ7.0 to 22.2Ϯ8.7 mL/min/dL, Pϭ0.003) indicating impaired microvascular function. Bed rest decreased brachial artery diameter and increased systolic blood pressure suggesting increased basal arterial tone. There were no changes in circulating inflammatory markers arguing against systemic inflammation as a mechanism for vascular dysfunction in this setting. Conclusions-Physical inactivity was associated with the development of insulin resistance, dyslipidemia, increased blood pressure, and impaired microvascular function in healthy volunteers. 3 Despite compelling evidence that physical inactivity is detrimental to cardiovascular health, over one quarter of all Americans engage in no leisure time physical activity. 4 The pathways leading from a sedentary lifestyle to insulin resistance and atherosclerosis are incompletely understood.Dysfunction of the vascular endothelium contributes to atherogenesis 5 and has been linked to sedentary lifestyle. In cross-sectional studies, sedentary individuals have impaired endothelial vasomotor function compared with those who are physically active. 6 Sedentary individuals also display impaired reactive hyperemia, 7 which is the increase in blood flow that occurs after transient ischemia and is a complex response that reflects both endothelium-dependent and endothelium-independent dilation of resistance vessels. 8 States of insulin resistance, including type 2 diabetes mellitus and obesity, are also associated with endothelial dysfunction. 9 Previous studies have demonstrated that short periods of inactivity lead to insulin resistance in humans. 10 -12 We hypothesized that insulin resistance induced by short-term physical inactivity would be associated with vascular dysfunction. This finding would lend further support to basic studies suggesting that insulin resistance and vascular dysfunction share common mechanisms. 13 Thus, we assessed vascular function and glucose tolerance before and after a 5-day period of strict bed rest in healthy subjects. Materials and Methods SubjectsHealthy nonsmoking volunteers were recruited for this study by newspaper and internet advertisement. Subjects were eligible if they had no clinical history of hypertension, diabetes mellitus, or hyperlipidemia, and were not taking any prescription medications. We sought individuals with preserved ...

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“…BH4 significantly improves endothelium-dependent vasodilatation in old subjects suggesting that in humans, vascular aging in healthy subjects is associated with loss of BH4 rather than L-arginine. 12 Oxidation of BH4 in human arteries is most likely caused by reported increase in activity of NADPH oxidase and subsequent formation of peroxynitrite. 13 Indeed, peroxynitrite is a very potent oxidant of BH4.…”

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confidence: 99%

Mechanisms of Endothelial Dysfunction Induced by Aging

Katušić

2007

Circulation Research

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Tetrahydrobiopterin augments endothelium‐dependent dilatation in sedentary but not in habitually exercising older adults

Cited by 154 publications

References 62 publications

Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults

Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults

Physical Inactivity Rapidly Induces Insulin Resistance and Microvascular Dysfunction in Healthy Volunteers

Mechanisms of Endothelial Dysfunction Induced by Aging

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