The Arteriolar Glycocalyx Plays a Role in the Regulation of Blood Flow in the Iliac of the Anaesthetised Pig

Physiological Research ◽

10.33549/physiolres.933630 ◽

2018 ◽

pp. 41-44 ◽

Cited By ~ 2

Author(s):

T. RUANE-O’HORA ◽

F. MARKOS

Keyword(s):

Blood Flow ◽

Iliac Artery ◽

Flow Measurement ◽

Flow Resistance ◽

Vascular Conductance ◽

Vascular Bed ◽

Resistance Vessels ◽

Flow Pressure

The role of the glycocalyx of arterial resistance vessels in regulating blood flow in vivo is not fully understood. Therefore, the effect of glycocalyx damage using two separate compounds, hyaluronidase and N-Formylmethionyl-leucyl-phenylalanine (fMLP), was evaluated in the iliac artery vascular bed of the anaesthetised pig. Blood flow and pressure were measured in the iliac, an adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3 occlusions at 3-4 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and vascular conductance (flow/pressure) was calculated. Saline, hyaluronidase (14 and 28 µg/ml/min), and fMLP (1 µM/min) were infused separately, downstream of the adjustable snare and their effect on arterial conductance assessed. Hyaluronidase at the higher infusion rate and fMLP both caused a reduction in arterial conductance, and hence an increase in blood flow resistance. In conclusion, the results show that glycocalyx damage causes an increase in resistance to blood flow in the iliac artery vascular bed.

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Immediate Direct Peripheral Vasoconstriction in Response to Hyperinsulinemia and Metformin in the Anesthetized Pig

Physiological Research ◽

10.33549/physiolres.932736 ◽

2014 ◽

pp. 559-566 ◽

Cited By ~ 1

Author(s):

F. MARKOS ◽

C. M. SHORTT ◽

D. EDGE ◽

T. RUANE-O’HORA ◽

M. I. M. NOBLE

Keyword(s):

Blood Flow ◽

Flow Measurement ◽

Direct Action ◽

Vascular Effects ◽

Control Blood Glucose ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Flow Pressure

Elevated levels of insulin have been reported to induce both an arterial vasodilation mediated by nitric oxide (NO), and vasoconstriction mediated by endothelin and reactive oxygen radicals. Metformin, used to control blood glucose levels in type 2 diabetes, has also been shown to cause NO-mediated dilation of conduit arteries. It is possible that these contradictory vascular effects are due to a non-direct action on arteries. Therefore, the direct effect of high levels of insulin and metformin infusion on resistance artery diameter was evaluated. Experiments were carried out on the anesthetized pig; blood flow and pressure were measured in the iliac artery. An adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3-4 occlusions at 5 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and the conductance (∆flow / ∆pressure) calculated. Saline, insulin (20 and 40 mUSP/l/min), and metformin (1 µg/ml/min) were infused separately downstream of the adjustable snare and their effect on arterial conductance assessed. Insulin at both infusion rates and metformin caused a significant reduction in peripheral vascular conductance. In conclusion, hyperinsulinemia and metformin infusion constrict resistance arterial vessels in vivo.

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Regional blood flow measurement in vivo for a definable geometry

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1964.206.5.962 ◽

1964 ◽

Vol 206 (5) ◽

pp. 962-966 ◽

Cited By ~ 8

Author(s):

Marvin B. Bacaner ◽

James S. Beck

Keyword(s):

Blood Flow ◽

Flow Measurement ◽

Necessary Conditions ◽

Regional Blood Flow ◽

The Body ◽

Continuous Measure ◽

Radioisotope Method ◽

Arterial Concentration ◽

Regional Concentration

A radioisotope method for measuring regional blood flow in the intestine of the dog in vivo has been favorably compared with measurement by timed collection of total venous outflow. The necessary conditions are a continuous measure of arterial concentration and cumulative regional concentration of radioisotope, an experimentally definable region, and temporary complete retention of tracer. The derivation of the relations used suggests additional applications of the method to other regions of the body.

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METTL3-dependent N6-methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2025070118 ◽

2021 ◽

Vol 118 (7) ◽

pp. e2025070118

Author(s):

Chian-Shiu Chien ◽

Julie Yi-Shuan Li ◽

Yueh Chien ◽

Mong-Lien Wang ◽

Aliaksandr A. Yarmishyn ◽

...

Keyword(s):

Blood Flow ◽

Endothelial Activation ◽

Plaque Formation ◽

Rna Modification ◽

Branch Points ◽

Monocyte Adhesion ◽

Down Regulation ◽

Hemodynamic Forces

Atherosclerosis is characterized by the plaque formation that restricts intraarterial blood flow. The disturbed blood flow with the associated oscillatory stress (OS) at the arterial curvatures and branch points can trigger endothelial activation and is one of the risk factors of atherosclerosis. Many studies reported the mechanotransduction related to OS and atherogenesis; however, the transcriptional and posttranscriptional regulatory mechanisms of atherosclerosis remain unclear. Herein, we investigated the role of N6-methyladenosine (m6A) RNA methylation in mechanotransduction in endothelial cells (ECs) because of its important role in epitranscriptome regulation. We have identified m6A methyltransferase METTL3 as a responsive hub to hemodynamic forces and atherogenic stimuli in ECs. OS led to an up-regulation of METTL3 expression, accompanied by m6A RNA hypermethylation, increased NF-κB p65 Ser536 phosphorylation, and enhanced monocyte adhesion. Knockdown of METTL3 abrogated this OS-induced m6A RNA hypermethylation and other manifestations, while METTL3 overexpression led to changes resembling the OS effects. RNA-sequencing and m6A-enhanced cross-linking and immunoprecipitation (eCLIP) experiments revealed NLRP1 and KLF4 as two hemodynamics-related downstream targets of METTL3-mediated hypermethylation. The METTL3-mediated RNA hypermethylation up-regulated NLRP1 transcript and down-regulated KLF4 transcript through YTHDF1 and YTHDF2 m6A reader proteins, respectively. In the in vivo atherosclerosis model, partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP3 up-regulation, and KLF4 down-regulation. Collectively, we have demonstrated that METTL3 serves a central role in the atherogenesis induced by OS and disturbed blood flow.

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Blood flow measurement in the in vivo mouse model by the combination of Doppler OCT and the signal power decrease in spectral domain OCT

10.1117/12.831836 ◽

2009 ◽

Author(s):

Julia Walther ◽

Gregor Mueller ◽

Henning Morawietz ◽

Edmund Koch

Keyword(s):

Blood Flow ◽

Mouse Model ◽

Flow Measurement ◽

Spectral Domain ◽

Signal Power ◽

Blood Flow Measurement ◽

Spectral Domain Oct ◽

Doppler Oct

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Abstract 062: Regulation of Nephron Afferent Arteriole Resistance in Obesity: Role of Connecting Tubule Glomerular Feedback

Hypertension ◽

10.1161/hyp.68.suppl_1.062 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Sumit R Monu ◽

Mani Maheshwari ◽

Hong Wang ◽

Ed Peterson ◽

Oscar Carretero

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Tubuloglomerular Feedback ◽

Afferent Arteriole ◽

Connecting Tubule ◽

Single Nephron ◽

Renal Micropuncture ◽

The Difference

In obesity, renal damage is caused by increase in renal blood flow (RBF), glomerular capillary pressure (P GC ), and single nephron glomerular filtration rate but the mechanism behind this alteration in renal hemodynamics is unclear. P GC is controlled mainly by the afferent arteriole (Af-Art) resistance. Af-Art resistance is regulated by mechanism similar to that in other arterioles and in addition, it is regulated by two intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to an increase in sodium chloride (NaCl) in the macula densa, via sodium–potassium-2-chloride cotransporter-2 (NKCC2) and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation and is mediated by connecting tubule via epithelial sodium channel (ENaC). CTGF is blocked by the ENaC inhibitor benzamil. Attenuation of TGF reduces Af-Art resistance and allows systemic pressure to get transmitted to the glomerulus that causes glomerular barotrauma/damage. In the current study, we tested the hypothesis that TGF is attenuated in obesity and that CTGF contributes to this effect. We used Zucker obese rats (ZOR) while Zucker lean rats (ZLR) served as controls. We performed in-vivo renal micropuncture of individual rat nephrons while measuring stop-flow pressure (P SF ), an index of P GC. TGF response was measured as a decrease in P SF induced by changing the rate of late proximal perfusion from 0 to 40nl/min in stepwise manner.CTGF was calculated as the difference of P SF value between vehicle and benzamil treatment, at each perfusion rate. Maximal TGF response was significantly less in ZOR (6.16 ± 0.52 mmHg) when compared to the ZLR (8.35 ± 1.00mmHg), p<0.05 , indicating TGF resetting in the ZOR. CTGF was significantly higher in ZOR (6.33±1.95 mmHg) when compared to ZLR (1.38±0.89 mmHg), p<0.05 . When CTGF was inhibited with the ENaC blocker Benzamil (1μM), maximum P SF decrease was 12.30±1.72 mmHg in ZOR and 10.60 ± 1.73 mmHg in ZLR, indicating that blockade of CTGF restored TGF response in ZOR. These observations led us to conclude that TGF is reset in ZOR and that enhanced CTGF contributes to this effect. Increase in CTGF may explain higher renal blood flow, increased P GC and higher glomerular damage in obesity.

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Mechanical factors and the regulation of perfusion through atelectatic lung in pigs

Journal of Applied Physiology ◽

10.1152/jappl.1982.52.3.647 ◽

1982 ◽

Vol 52 (3) ◽

pp. 647-654 ◽

Cited By ~ 6

Author(s):

S. Enjeti ◽

P. B. Terry ◽

H. A. Menkes ◽

R. J. Traystman

Keyword(s):

Blood Flow ◽

Vascular Conductance ◽

Hemodynamic Responses ◽

Closed Chest ◽

Open Chest ◽

Regional Hemodynamics ◽

Mechanical Factors

The role of mechanical interdependence in the perfusion of atelectatic lung was studied in two ways: a) regional hemodynamics were compared before (control) and after the development of lobar and sublobar atelectasis, and b) the effect of thoracotomy on regional hemodynamics was assessed. With lobar atelectasis mean lobar blood flow and vascular conductance decreased to 60% of control. Sublobar atelectasis caused mean sublobar blood flow and vascular conductance to decrease to 6% of control. Opening the chest after production of lobar atelectasis caused blood flow to fall to 50% of control. When sublobar atelectasis was produced in the open chest, sublobar blood flow decreased to 25% of control measurements made prior to thoracotomy. We conclude that with a closed chest, sublobar vascular distortion mediated by mechanical interdependence may be an important mechanism responsible for the differences in hemodynamic responses to atelectasis between lobes and sublobar regions.

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Adenosine potentiates insulin-stimulated myocardial glucose uptake in vivo

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1988.254.5.h970 ◽

1988 ◽

Vol 254 (5) ◽

pp. H970-H975 ◽

Cited By ~ 7

Author(s):

W. R. Law ◽

R. M. Raymond

Keyword(s):

Blood Flow ◽

Glucose Uptake ◽

Coronary Blood Flow ◽

Metabolic Regulation ◽

Metabolic Response ◽

Dose Response Relationship ◽

Circumflex Artery ◽

Myocardial Glucose Uptake

Myocardial adenosine (ADO) has long been regarded as a regulator of coronary blood flow. In other tissues, such as adipose and skeletal muscle, much attention has focused on the role of ADO as a metabolic regulator of the actions of insulin. In the present study, we determined the effect of ADO infusion on insulin-stimulated myocardial glucose uptake (MGU). Mongrel dogs of either sex were instrumented to obtain arterial-coronary sinus differences for glucose, lactate, and oxygen. These were multiplied by circumflex artery blood flow (Q) to obtain uptake values. Measurements were made before and during hyperinsulinemic (4 U/min)-euglycemic clamp (clamp) with intracoronary infusions of saline, ADO, adenosine deaminase (ADA), or nitroprusside (NP). During clamp, MGU increased from a basal value of 3.0 +/- 0.8 mg/min (mean +/- SE) to 5.53 +/- 0.8 mg/min. Adenosine infusion potentiated this response, raising MGU further to 9.02 +/- 1.1 mg/min while not significantly affecting lactate or oxygen uptakes. Infusion of ADA confirmed the specificity of the response by blocking the metabolic effect of exogenously infused ADO. When NP was infused, Q increased significantly without altering MGU, indicating that the metabolic response to ADO was independent of the changes it caused in Q. A dose-response relationship existed between ADO and insulin-stimulated MGU. The metabolic response to ADO was more sensitive than the vasodilator response. It is concluded that ADO acts as a regulator of insulin in heart. This metabolic regulation occurs independent of changes in coronary blood flow.

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Influence of dehydration on locally mediated hindlimb vasodilation in baboons

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1988.255.2.h266 ◽

1988 ◽

Vol 255 (2) ◽

pp. H266-H271

Author(s):

R. M. Thornton ◽

D. W. Proppe

Keyword(s):

Blood Flow ◽

Iliac Artery ◽

Water Deprivation ◽

Arterial Occlusion ◽

External Iliac Artery ◽

Artery Blood Flow ◽

Vascular Conductance ◽

Similar Reduction ◽

Arterial Blood ◽

Cutaneous Vasodilation

Previous studies indicate that the heat stress-induced cutaneous vasodilation in baboons is attenuated during dehydration by mechanisms other than the well-known neurohumoral vasoconstrictor mechanisms. Therefore, this study sought to determine whether dehydration also attenuates locally mediated maximum hindlimb blood flow and vascular conductance in baboons. Five baboons were chronically instrumented to measure arterial blood pressure and mean external iliac artery blood flow (MIBF). Hindlimb vasodilation was induced by occlusions of the external iliac artery for 2.5, 5.0, 7.5, and 10.0 min and by close-arterial injections of acetylcholine (ACh) and sodium nitroprusside (NP) in graded doses. These vasodilatory stimuli were applied in euhydrated and dehydrated states, the latter being produced by water deprivation for 64-68 h. Maximum MIBF and iliac vascular conductance (IVC) after arterial occlusion were reduced by 67–70% during dehydration. Also, maximum MIBF and IVC produced by ACh in the dehydrated state were 46–;52% lower than in the euhydrated state. A similar reduction in the responses to NP occurred during dehydration. It is concluded that the maximum hindlimb blood flow and vascular conductance produced by local, nonneurohumoral mechanisms are attenuated in the baboon during dehydration.

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Vascular Stents Coated with Electrospun Drug-Eluting Material: Functioning in Rabbit Iliac Artery

Polymers ◽

10.3390/polym12081741 ◽

2020 ◽

Vol 12 (8) ◽

pp. 1741

Author(s):

Konstantin A. Kuznetsov ◽

Ivan S. Murashov ◽

Vera S. Chernonosova ◽

Boris P. Chelobanov ◽

Alena O. Stepanova ◽

...

Keyword(s):

Blood Flow ◽

Iliac Artery ◽

Balloon Catheter ◽

Bare Metal Stents ◽

Blood Flow Rate ◽

Metal Stents ◽

Bare Metal ◽

Vascular Stents ◽

Drug Eluting

A stenting procedure aimed at blood flow restoration in stenosed arteries significantly improves the efficiency of vascular surgery. However, the current challenge is to prevent neointimal growth, which reduces the vessel lumen, in the stented segments in the long run. We tested in vivo drug-eluting coating applied by electrospinning to metal vascular stents to inhibit the overgrowth of neointimal cells via both the drug release and mechanical support of the vascular wall. The blend of polycaprolactone with human serum albumin and paclitaxel was used for stent coating by electrospinning. The drug-eluting stents (DESs) were placed using a balloon catheter to the rabbit common iliac artery for 1, 3, and 6 months. The blood flow rate was ultrasonically determined in vivo. After explantation, the stented arterial segment was visually and histologically examined. Any undesirable biological responses (rejection or hemodynamically significant stenosis) were unobservable in the experimental groups. DESs were less traumatic and induced weaker neointimal growth; over six months, the blood flow increased by 37% versus bare-metal stents, where it increased by at least double the rate. Thus, electrospun-coated DESs demonstrate considerable advantages over the bare-metal variants.

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