Arterial Function in Cardio-Metabolic Diseases: From the Microcirculation to the Large Conduits

Chantler, Paul D.; Frisbee, Jefferson C.

doi:10.1016/j.pcad.2014.09.005

Cited by 25 publications

(37 citation statements)

References 93 publications

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“…Oxidative stress is known to play an important role in the pathogenesis of vascular dysfunction (50). Not only does a prooxidative stress [reactive oxygen species (ROS)] environment impact the NO pathway and its regulation of arterial remodeling, but ROS can independently interact with the components of the perivascular matrix and drive collagen cross-linking, collagen deposition, and the fracturing of elastin (8). Previous evidence suggests that eutrophic inward remodeling was dependent on ROS activation of specific matrix metalloproteinases (that degrade and reorganize the extracellular matrix of the vessel wall) (36).…”

Section: Discussionmentioning

confidence: 99%

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats

Brooks

DeVallance

d’Audiffret

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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-The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7-8, 12-13, and 16 -17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7-8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS. metabolic syndrome; cerebrovascular remodeling; arterial stiffness; reactive oxygen species NEW & NOTEWORTHY We describe the temporal development of alterations in wall mechanics and vascular reactivity of middle cerebral arteries of obese Zucker rats through evolution of the metabolic syndrome. While novel, this study is particularly noteworthy, as we also use clinically relevant agents against the metabolic syndrome given from an early age to determine vascular outcomes.THE METABOLIC SYNDROME (MetS), a clustering of metabolic abnormalities such as obesity, impaired glycemic control, atherogenic dyslipidemia, and hypertension, with the additional contributing conditions of a prooxidant, prothrombotic, and proinflammatory state, is prevalent in ϳ56 million adults in the United States (21). Correspondingly, MetS is associated with a threefold increased risk of cardiovascular mortality (21) and a 50% increased risk of stroke (5) and is a known risk factor for cognitive decline with aging (41). It is therefore imperative that translationally relevant models of MetS be effectively interrogated to guide our understanding of the cerebrovascular adaptations that are associated with the development of MetS, its physiological, molecular, and genomic mechanistic underpinnings, and the effectiveness of established and novel therapeutic agents in either blunti...

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Section: Discussionmentioning

confidence: 99%

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats

Brooks

DeVallance

d’Audiffret

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…46 With increased stiffness in large vessels, the pulsatile pressure/flow of the left ventricular ejection (which is normally transformed in a continuous flow) moves downstream to the small vessels of the arterial tree. 46,47 The chronic increase in BP along with the mechanical stress on the vascular wall and inflammation are postulated to induce remodeling of the muscular vessel wall, mainly in small arterioles, but also in precapillary resistance vessels, leading to luminal restrictions and capillary rarefaction. 7,46,47 Microvascular rarefaction can reduce the vessel surface area available for oxygen delivery and increase the diffusional distance between vessels and their target cells, reducing blood-to-cell oxygen transfer, leading to tissue ischemia.…”

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confidence: 99%

Impaired Muscle Oxygenation and Elevated Exercise Blood Pressure in Hypertensive Patients

et al. 2017

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E ssential hypertension is characterized by sustained elevations of blood pressure (BP) that can lead to target organ damage and an increased risk for cardiovascular disease. 1Potential life-threatening outcomes of hypertension, such as stroke, renal insufficiency, and cardiac hypertrophy, had been initially perceived as a result of macrovascular alterations. These macrovascular events, however, do not occur independently of microvascular derangement. [2][3][4] Studies have shown that alterations in microvascular structure (rarefaction), vasomotor tonus (enhanced vasoconstriction or blunted vasodilation), and endothelial dysfunction are principal processes in the pathogenesis of hypertension and are evident in several organs/tissue types. [5][6][7][8] In the skeletal muscle, microvascularization is important for oxygen and nutrient supply and for effective metabolite clearance. Studies in hypertension have shown structural or functional impairments in the microvasculature within skeletal muscles, 8 implying a reduced capacity for oxygen delivery and exchange. Furthermore, animal studies using experimental models of hypertension suggested that mitochondrial dysfunction (ie, decreased expression of mitochondrial components and defects in respiratory complexes) and increased oxidative stress result in impaired oxidative capacity and reduced mitochondrial ATP production.9,10 Importantly, in these animals, the mitochondrial dysfunction and the reduced oxidative capacity were present before the development of hypertension, suggesting a possible role of these processes to the pathogenesis of hypertension.11 However, information on skeletal muscle microvascular alterations and oxidative Abstract-This study examined in vivo (1) skeletal muscle oxygenation and microvascular function, at rest and during handgrip exercise, and (2) their association with macrovascular function and exercise blood pressure (BP), in newly diagnosed, never-treated patients with hypertension and normotensive individuals. Ninety-one individuals (51 hypertensives and 40 normotensives) underwent office and 24-hour ambulatory BP, arterial stiffness, and central aortic BP assessment, followed by a 5-minute arterial occlusion and a 3-minute submaximal handgrip exercise. Changes in muscle oxygenated and deoxygenated hemoglobin and tissue oxygen saturation were continuously monitored by nearinfrared spectroscopy and beat-by-beat BP by Finapres. Hypertensives had higher (P<0.001) central aortic BP and pulse wave velocity versus normotensives and exhibited (1) a blunted tissue oxygen saturation response during occlusion, with slower (P=0.006) deoxygenation rate, suggesting reduced muscle oxidative capacity, and (2) a slower reoxygenation rate and blunted hyperemic response (P<0.05), showing reduced microvascular reactivity. Muscle oxygenation responses were correlated with aortic systolic and pulse pressure and augmentation index (P<0.05; age and body mass index (BMI) adjusted). When exercising at the same submaximal intensity, hypertensives required a sig...

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“…At first, these adaptations are compensatory and aim to ensure adequate tissue perfusion in relation to higher metabolic requirement. However, in later stages, they become detrimental and contribute to accelerated risk for cardiovascular disorders (8). Increased blood flow and hypertension, usually associated with obesity, are correlated to arterial stiffness (8, 30).…”

Section: Discussionmentioning

confidence: 99%

“…Vascular disorders are central, involving morphological and functional remodeling of the arterial vasculature. Hemodynamic parameters are altered that imposes stress in the heart and other organs (8). Major changes are arterial stiffening (9), arterial wall thickening, and endothelial dysfunction (10).…”

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confidence: 99%

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Dietary supplementation with a specific melon concentrate reverses vascular dysfunction induced by cafeteria diet

Carillon

Jover

Cristol

et al. 2016

Food & Nutrition Research

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BackgroundObesity-related metabolic syndrome is associated with high incidence of cardiovascular diseases partially consecutive to vascular dysfunction. Therapeutic strategies consisting of multidisciplinary interventions include nutritional approaches. Benefits of supplementation with a specific melon concentrate, enriched in superoxide dismutase (SOD), have previously been shown on the development of insulin resistance and inflammation in a nutritional hamster model of obesity.ObjectiveWe further investigated arterial function in this animal model of metabolic syndrome and studied the effect of melon concentrate supplementation on arterial contractile activity.Design and resultsThe study was performed on a hamster model of diet-induced obesity. After a 15-week period of cafeteria diet, animals were supplemented during 4 weeks with a specific melon concentrate (Cucumis melo L.) Contractile responses of isolated aorta to various agonists and antagonists were studied ex vivo. Cafeteria diet induced vascular contractile dysfunction associated with morphological remodeling. Melon concentrate supplementation partially corrected these dysfunctions; reduced morphological alterations; and improved contractile function, especially by increasing nitric oxide bioavailability and expression of endogenous SOD.ConclusionsSupplementation with the specific melon concentrate improves vascular dysfunction associated with obesity. This beneficial effect may be accounted for by induction of endogenous antioxidant defense. Such an approach in line with nutritional interventions could be a useful strategy to manage metabolic syndrome–induced cardiovascular trouble.

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Arterial Function in Cardio-Metabolic Diseases: From the Microcirculation to the Large Conduits

Cited by 25 publications

References 93 publications

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats

Impaired Muscle Oxygenation and Elevated Exercise Blood Pressure in Hypertensive Patients

Dietary supplementation with a specific melon concentrate reverses vascular dysfunction induced by cafeteria diet

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