Vascular wall reactivity in conductance and resistance arteries: differential effects of insulin resistance

O’Brien, Sheila F; McKendrick, Joyce D.; Radomski, Marek W.; Davidge, Sandra T.; Russell, James C.

doi:10.1139/cjpp-76-1-72

Cited by 10 publications

(9 citation statements)

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“…In addition, male JCR-LA-cp rats develop atherosclerosis and myocardial ischemia. Vascular responses and endothelial function were studied by O'Brien and coworkers [146] rendering similar results as for micro- versus macrovascular endothelial dysfunction as those of SHROB rats, although the latter displayed a more intense impairment of acetylcholine responses. …”

Section: Animal Models Of Metabolic Syndrome: Vascular Functionmentioning

confidence: 86%

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Hypertension in Metabolic Syndrome: Vascular Pathophysiology

Mendizábal

Lloréns

Nava

2013

International Journal of Hypertension

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Metabolic syndrome is a cluster of metabolic and cardiovascular symptoms: insulin resistance (IR), obesity, dyslipemia. Hypertension and vascular disorders are central to this syndrome. After a brief historical review, we discuss the role of sympathetic tone. Subsequently, we examine the link between endothelial dysfunction and IR. NO is involved in the insulin-elicited capillary vasodilatation. The insulin-signaling pathways causing NO release are different to the classical. There is a vasodilatory pathway with activation of NO synthase through Akt, and a vasoconstrictor pathway that involves the release of endothelin-1 via MAPK. IR is associated with an imbalance between both pathways in favour of the vasoconstrictor one. We also consider the link between hypertension and IR: the insulin hypothesis of hypertension. Next we discuss the importance of perivascular adipose tissue and the role of adipokines that possess vasoactive properties. Finally, animal models used in the study of vascular function of metabolic syndrome are reviewed. In particular, the Zucker fatty rat and the spontaneously hypertensive obese rat (SHROB). This one suffers macro- and microvascular malfunction due to a failure in the NO system and an abnormally high release of vasoconstrictor prostaglandins, all this alleviated with glitazones used for metabolic syndrome therapy.

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Section: Animal Models Of Metabolic Syndrome: Vascular Functionmentioning

confidence: 86%

“…This rat is homozygous for the autosomal recessive cp gene (cp/cp) and is obese, hyperphagic, insulin resistant, hyperinsulinemic, and hypertriglyceridemic [146]. In addition, male JCR-LA-cp rats develop atherosclerosis and myocardial ischemia.…”

Section: Animal Models Of Metabolic Syndrome: Vascular Functionmentioning

confidence: 99%

Hypertension in Metabolic Syndrome: Vascular Pathophysiology

Mendizábal

Lloréns

Nava

2013

International Journal of Hypertension

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“…This similarity also applies to the discrepant findings obtained in various vascular beds in different models of obesity (Table 1). In the obese, JCR:LA-cp rats, an impaired endothelium-dependent relaxation of aorta to A23187 (17) and reduced dilations of mesenteric arteries to ACh (118) have been reported. Reduced mesenteric (112) and skeletal muscle (41) arteriolar dilation to ACh was also found in rats fed a high-fat diet.…”

Section: Impact Of Obesity On Coronary Vasodilator Functionmentioning

confidence: 97%

Mechanisms of coronary microvascular adaptation to obesity

Bagi¹

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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The metabolic syndrome (MetS) is associated with clustering of cardiovascular risk factors in individuals that may greatly increase their risk of developing coronary artery disease. Obesity and related metabolic dysfunction are the driving forces in the prevalence of MetS. It is believed that obesity has detrimental effects on cardiovascular function, but its overall impact on the vasomotor regulation of small coronary arteries is still debated. Emerging evidence indicates that in obesity coronary arteries adapt to hemodynamic changes via maintaining and/or upregulating cellular mechanism(s) intrinsic to the vascular wall. Among other factors, endothelial production of cyclooxygenase-2-derived prostacyclin and reactive oxygen species, as well as increased nitric oxide sensitivity and potassium channel activation in smooth muscle cells, have been implicated in maintaining coronary vasodilator function. This review aims to examine studies that have been primarily focused on alterations in coronary vasodilator function in obesity. A better understanding of cellular mechanisms that may contribute to coronary microvascular adaptation may provide insight into the sequence of pathological events in obesity and may allow the harnessing of these effects for therapeutic purposes.

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“…Impaired endothelium-dependent function is also observed in various animal models of obesity, including obese Zucker [11,12] and JCR:LA-cp rats [13], and rats fed a high-fat diet [14][15][16]. However, the mechanisms underlying endothelial dysfunction in obesity are unclear.…”

Section: Introductionmentioning

confidence: 99%

Disrupted endothelial cell heterogeneity and network organization impair vascular function in prediabetic obesity

et al. 2020

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Background: Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations that give rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfunction are ill-defined. Increasing evidence suggests that endothelial cells are not a population of uniform cells but are highly heterogeneous and are organized as a communicating multicellular network that controls vascular function. Purpose: To investigate the hypothesis that disrupted endothelial heterogeneity and network-level organization contribute to impaired vascular reactivity in obesity. Methods and results: To study obesity-related vascular function without complications associated with diabetes, a state of prediabetic obesity was induced in rats. Small artery diameter recordings confirmed nitric-oxide mediated vasodilator responses were dependent on increases in endothelial calcium levels and were impaired in obese animals. Single-photon imaging revealed a linear relationship between blood vessel relaxation and population-wide calcium responses. Obesity did not alter the slope of this relationship, but impaired calcium responses in the endothelial cell network. The network comprised structural and functional components. The structural architecture, a hexagonal lattice network of connected cells, was unchanged in obesity. The functional network contained sub-populations of clustered specialized agonist-sensing cells from which signals were communicated through the network. In obesity there were fewer but larger clusters of sensory cells and communication path lengths between clusters increased. Communication between neighboring cells was unaltered in obesity. Altered network organization resulted in impaired, population-level calcium signaling and deficient endothelial control of vascular tone. Conclusions: The distribution of cells in the endothelial network is critical in determining overall vascular response. Altered cell heterogeneity and arrangement in obesity decreases endothelial function and provides a novel framework for understanding compromised endothelial function in cardiovascular disease.

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Vascular wall reactivity in conductance and resistance arteries: differential effects of insulin resistance

Cited by 10 publications

References 0 publications

Hypertension in Metabolic Syndrome: Vascular Pathophysiology

Hypertension in Metabolic Syndrome: Vascular Pathophysiology

Mechanisms of coronary microvascular adaptation to obesity

Disrupted endothelial cell heterogeneity and network organization impair vascular function in prediabetic obesity

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