Hyperglycemia Stimulates a Sustained Increase in Hydraulic Conductivity In Vivo without Any Change in Reflection Coefficient

Perrin, Rachel M.; Harper, Steven J.; Corrall, R. J. M.; Bates, David O.

doi:10.1080/10739680701436129

Cited by 13 publications

(15 citation statements)

References 52 publications

(87 reference statements)

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“…Endothelial barrier function consists of two parts: the EC layer and the glycocalyx lining on ECs. The glycocalyx consists of a highly hydrated mesh of membrane-associated proteoglycans, glycosaminoglycans, glycoproteins, and glycolipids (35,36,39) and is a very dynamic structure. The endothelial glycocalyx contributes as much as 60% of the hydraulic resistance of the capillary wall (39).…”

Section: Discussionmentioning

confidence: 99%

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Endothelial barrier dysfunction in diabetic conduit arteries: a novel method to quantify filtration

Huxley

Kassab

2013

American Journal of Physiology-Heart and Circulatory Physiology

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The endothelial barrier plays an important role in atherosclerosis, hyperglycemia, and hypercholesterolemia. In the present study, an accurate, reproducible, and user-friendly method was used to further understand endothelial barrier function of conduit arteries. An isovolumic method was used to measure the hydraulic conductivity (L(p)) of the intact vessel wall and medial-adventitial layer. Normal arterial segments with diameters from 0.2 to 5.5 mm were used to validate the method, and femoral arteries of diabetic rats were studied as an example of pathological specimens. Various arterial segments confirmed that the volume flux of water per unit surface area was linearly related to intraluminal pressure, as confirmed in microvessels. L(p) of the intact wall varied from 3.5 to 22.1 × 10(-7) cm·s(-1)·cmH(2)O(-1) over the pressure range of 7-180 mmHg. Over the same pressure range, L(p) of the endothelial barrier changed from 4.4 to 25.1 × 10(-7) cm·s(-1)·cmH(2)O(-1). During perfusion with albumin-free solution, L(p) of rat femoral arteries increased from 6.1 to 13.2 × 10(-7) cm·s(-1)·cmH(2)O(-1) over the pressure range of 10-180 mmHg. Hyperglycemia increased L(p) of the femoral artery in diabetic rats from 2.9 to 5.5 × 10(-7) cm·s(-1)·cmH(2)O(-1) over the pressure range of 20-135 mmHg. In conclusion, the L(p) of a conduit artery can be accurately and reproducibly measured using a novel isovolumic method, which in diabetic rats is hyperpermeable. This is likely due to disruption of the endothelial glycocalyx.

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Section: Discussionmentioning

confidence: 99%

“…Hyperglycemia is a known culprit of microvascular hyperpermeability (19,36) and is thought to damage the glycocalyx overlaying the endothelium. Thus, hyperglycemia contributes to increased solute and volume flux (J v ) in the microvessels (11,31,32,43).…”

mentioning

confidence: 99%

Endothelial barrier dysfunction in diabetic conduit arteries: a novel method to quantify filtration

Huxley

Kassab

2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…23 The glycocalyx within arterioles is thought to protect the endothelial cells from the oscillating stresses of the cardiac cycle. 24 (3) The effect of hyperglycaemia on microvascular glycocalyx It was elegantly shown by Perrin et al 25 using the Landis and Michel method, that diabetic plasma, dialysed to 5 mM glucose concentration but containing high levels of VEGF and other macromolecules, had no effect on the calculated variable, hydraulic conductivity, i.e. the function of water filtration by glycocalyx.…”

Section: The Microvascular Glycocalyxmentioning

confidence: 98%

“…The calculations of Perrin et al 25 show that all the solute transfer can be accounted for by convective transfer, i.e. it is dependent on the increased water flux.…”

Section: The Microvascular Glycocalyxmentioning

confidence: 98%

Review: Hyperglycaemia and the vascular glycocalyx: the key to microalbuminuria and cardiovascular disease in diabetes mellitus?

Noble

Drake-Holland

2010

Diabetes & Vascular Disease

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T he vascular glycocalyx is a gel layer between endothelium and the blood, 0.5 µm thick. Evidence is presented from published studies to indicate that hyperglycaemia causes damage to the vascular glycocalyx. This damage results in microalbuminuria, excess fluid transfer to the interstitium, reduction in nitric oxide (NO) production by arterial endothelium, and leukocyte and platelet adhesion to endothelium leading to atherothrombosis. The lack of NO production proceeds from the fact that glycocalyx is the mechanotransducer transmitting the signal for increased shear stress between blood and arterial wall, and this function is inhibited by hyperglycaemia. When hyperinsulinaemia is also present, the problem is compounded by general arterial dilatation leading to low shear rates throughout the arterial tree. These findings explain the predisposition to atherothrombosis in the prediabetic condition of insulin resistance/metabolic syndrome/obesity and diabetes mellitus. It is proposed that greater efforts than ever are required to detect occult insulin resistance, to treat such patients and diabetics with ever more strict blood glucose control while minimising insulin levels, and to carry out further research into how glycocalyx structure and function can be preserved. Br J Diabetes Vasc Dis 2010;10:66-70

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“…After an incision of the thoracic cavity, the thoracic ducts were excised and placed in a petri dish containing cold (4 ° C) Krebsbicarbonate solution (KBS, in m M : 120.0 NaCl, 5.9 KCl, 2.5 CaCl 2 , 1.2 MgSO 4 , 1.2 NaH 2 PO 4 , 5 glucose, and 25.0 NaHCO 3 ). In the present study, we used KBS containing different concentrations of glucose (0, 0.1, 0.5, 1, 3, and 5 m M ), prepared by replacing glucose with equimolar amounts of mannitol [28]. With microsurgical instruments and an operating microscope, the thoracic ducts ( n = 55, maximum diameter of 340-657 µ m, and ~3 mm long) were isolated and then transferred to a 10-ml organ chamber with two glass micropipettes containing KBS with 0 m M glucose.…”

Section: Animalsmentioning

confidence: 99%

Glucose and Glucose Transporters Regulate Lymphatic Pump Activity through Activation of the Mitochondrial ATP-Sensitive K+ Channel

Li¹,

Mizuno²,

Ono³

et al. 2008

J. Physiol. Sci

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Abstract:We investigated the pivotal roles of glucose and its transporter in the regulation of mechanical activity of isolated rat thoracic ducts and then examined whether mitochondrial ATP-sensitive K + channels (mitoK ATP ) are involved in those responses. In the absence of extracellular glucose, the thoracic ducts showed pump activity during 120 min. Extracellular glucose caused a dose-dependent increase in the frequency of pump activity and a constriction in the thoracic ducts. Pump activity of the thoracic ducts in 0 m M glucose was completely inhibited in the presence of chlorogenic acid (an inhibitor of glucose-6-phosphatase). Cytochalasin B, an inhibitor of facilitative glucose transporter (GLUT), or phlorizin, an inhibitor of sodium-dependent glucose cotransporter (SGLT), significantly reduced the frequency of pump activity and dilated the thoracic ducts. A decrease in the frequency of pump activity induced by 5-hydroxydecanoate (5-HD, a selective blocker of mitoK ATP ) was completely reversed by ruthenium red (an inhibitor of Ca 2+ uniporter in mitochondria). Diazoxide (a selective opener of mitoK ATP ) significantly increased the frequency of pump activity. Carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP, a protonophore of mitochondrial proton pump action) significantly reduced the frequency of pump activity and dilated the thoracic ducts. Collectively, these findings suggest that glucose derived from intracellular glycogen and/or through GLUT/SGLT in lymphatic smooth muscles contributes to the regulation of the pump activity of isolated rat thoracic ducts, and that mitoK ATP in the cells may partially serve as a modulator of the mechanical functions associated with mitochondrial Ca 2+ uptake.

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Hyperglycemia Stimulates a Sustained Increase in Hydraulic Conductivity In Vivo without Any Change in Reflection Coefficient

Cited by 13 publications

References 52 publications

Endothelial barrier dysfunction in diabetic conduit arteries: a novel method to quantify filtration

Endothelial barrier dysfunction in diabetic conduit arteries: a novel method to quantify filtration

Review: Hyperglycaemia and the vascular glycocalyx: the key to microalbuminuria and cardiovascular disease in diabetes mellitus?

Glucose and Glucose Transporters Regulate Lymphatic Pump Activity through Activation of the Mitochondrial ATP-Sensitive K+ Channel

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