Mechanical Properties of Active and Passive Rat Middle Cerebral Arteries

Author(s):  
Rebecca J. Coulson ◽  
Marilyn J. Cipolla ◽  
Lisa Vitullo ◽  
Naomi C. Chesler

Cerebral arteries play an important role in the regulation of cerebral blood flow through autoregulation, a well established phenomenon which is caused by a combination of myogenic, neuronal and metabolic mechanisms [1]. Myogenic reactivity is the ability of the vascular smooth muscle cells (SMC) to contract in response to stretch or to an increase in transmural pressure (TMP), and to dilate in response to a decrease in TMP [2]. It is this active constriction of arteries within the autoregulatory range that prompts studies of not just passive mechanical properties, but also active mechanical properties. Passive properties provide an understanding of the behavior of the extracellular matrix components of arteries (i.e. collagen and elastin); but, in order to understand how the artery behaves in vivo, it is necessary to understand the mechanical properties with smooth muscle cell activation. Mechanical properties might also be altered if the vessel is diseased or damaged. Ischemia has been shown to reduce vascular tone, which might lead to brain tissue damage during stroke [3]. Therefore studying the mechanical properties of vessels in disease states to determine if they are able to adequately take part in controlling local blood flow is also important.

2015 ◽  
Vol 137 (11) ◽  
Author(s):  
Christine L. de Lancea ◽  
Tim David ◽  
Jordi Alastruey ◽  
Richard G. Brown

Blood flow through a vessel depends upon compliance and resistance. Resistance changes dynamically due to vasoconstriction and vasodilation as a result of metabolic activity, thus allowing for more or less flow to a particular area. The structure responsible for directing blood to the different areas of the brain and supplying the increase flow is the cerebral arterial circle (CAC). A series of 1D equations were utilized to model propagating flow and pressure waves from the left ventricle of the heart to the CAC. The focus of the current research was to understand the collateral capability of the circle. This was done by decreasing the peripheral resistance in each of the efferent arteries, up to 10% both unilaterally and bilaterally. The collateral patterns were then analyzed. After the initial 60 simulations, it became apparent that flow could increase beyond the scope of a 10% reduction and still be within in vivo conditions. Simulations with higher percentage decreases were performed such that the same amount of flow increase would be induced through each of the efferent arteries separately, same flow tests (SFTs), as well as those that were found to allow for the maximum flow increase through the stimulated artery, maximum flow tests (MFTs). The collateral pattern depended upon which efferent artery was stimulation and if the stimulation was unilaterally or bilaterally induced. With the same amount of flow increase through each of the efferent arteries, the MCAs (middle cerebral arteries) had the largest impact on the collateral capability of the circle, both unilaterally and bilaterally.


Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 778 ◽  
Author(s):  
Ruben Daum ◽  
Dmitri Visser ◽  
Constanze Wild ◽  
Larysa Kutuzova ◽  
Maria Schneider ◽  
...  

Appropriate mechanical properties and fast endothelialization of synthetic grafts are key to ensure long-term functionality of implants. We used a newly developed biostable polyurethane elastomer (TPCU) to engineer electrospun vascular scaffolds with promising mechanical properties (E-modulus: 4.8 ± 0.6 MPa, burst pressure: 3326 ± 78 mmHg), which were biofunctionalized with fibronectin (FN) and decorin (DCN). Neither uncoated nor biofunctionalized TPCU scaffolds induced major adverse immune responses except for minor signs of polymorph nuclear cell activation. The in vivo endothelial progenitor cell homing potential of the biofunctionalized scaffolds was simulated in vitro by attracting endothelial colony-forming cells (ECFCs). Although DCN coating did attract ECFCs in combination with FN (FN + DCN), DCN-coated TPCU scaffolds showed a cell-repellent effect in the absence of FN. In a tissue-engineering approach, the electrospun and biofunctionalized tubular grafts were cultured with primary-isolated vascular endothelial cells in a custom-made bioreactor under dynamic conditions with the aim to engineer an advanced therapy medicinal product. Both FN and FN + DCN functionalization supported the formation of a confluent and functional endothelial layer.


1991 ◽  
Vol 11 (1) ◽  
pp. 161-164 ◽  
Author(s):  
Mária Faragó ◽  
Csaba Szabó ◽  
Eörs Dóra ◽  
Ildikó Horváth ◽  
Arisztid G. B. Kovách

To clarify the effect of extracellular magnesium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2+ concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by 10−8-10−5 M norepinephrine, were significantly potentiated at low Mg2+ (0.8 m M v. the normal, 1.2 m M). High (1.6 and 2.0 m M) Mg2+ exhibited an inhibitory effect on the contractile responses. No significant changes, however, in the EC50 values for norepinephrine were found. The endothelium-dependent relaxations induced by 108–10−5 M acetylcholine were inhibited by high (1.6 and 2.0 m M) Mg2+. Lowering of the Mg2+ concentration to 0.8 m M or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilatory responses also shifted the EC50 values for acetylcholine to the right. The present results show that the contractile responses of the cerebral arteries are extremely susceptible to the changes of Mg2+ concentrations. In response to contractile and endothelium-dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endothelial receptor. Since Mg2+ deficiency might facilitate the contractile but not the endothelium-dependent relaxant responses, the present study supports a role for Mg2+ deficiency in the development of the cerebral vasospasm.


2001 ◽  
Vol 1 ◽  
pp. 168-180 ◽  
Author(s):  
Lars Edvinsson ◽  
Peter J. Goadsby ◽  
Rolf Uddman

Amylin and adrenomedullin are two peptides structurally related to calcitonin gene-related peptide (CGRP). We studied the occurrence of amylin in trigeminal ganglia and cerebral blood vessels of the cat with immunocytochemistry and evaluated the role of amylin and adrenomedullin in the cerebral circulation by in vitro and in vivo pharmacology. Immunocytochemistry revealed that numerous nerve cell bodies in the trigeminal ganglion contained CGRP immunoreactivity (-ir); some of these also expressed amylin-ir but none adrenomedullin-ir. There were numerous nerve fibres surrounding cerebral blood vessels that contained CGRP-ir. Occasional fibres contained amylin-ir while we observed no adrenomedullin-ir in the vessel walls. With RT-PCR and Real-Time�PCR we revealed the presence of mRNA for calcitonin receptor-like receptor (CLRL) and receptor-activity-modifying proteins (RAMPs) in cat cerebral arteries. In vitro studies revealed that amylin, adrenomedullin, and CGRP relaxed ring segments of the cat middle cerebral artery. CGRP and amylin caused concentration-dependent relaxations at low concentrations of PGF2a-precontracted segment (with or without endothelium) whereas only at high concentration did adrenomedullin cause relaxation. CGRP8-37 blocked the CGRP and amylin induced relaxations in a parallel fashion. In vivo studies of amylin, adrenomedullin, and CGRP showed a brisk reproducible increase in local cerebral blood flow as examined using laser Doppler flowmetry applied to the cerebral cortex of the a-chloralose�anesthetized cat. The responses to amylin and CGRP were blocked by CGRP8-37. The studies suggest that there is a functional sub-set of amylin-containing trigeminal neurons which probably act via CGRP receptors.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hyun Ku Lee ◽  
Sang-Kwan Moon ◽  
Chul Jin ◽  
Seung-Yeon Cho ◽  
Seong-Uk Park ◽  
...  

The Governing Vessel 14 (GV14) (Dazhui) is one of the acupuncture points referred to as “seven acupoints for stroke.” Nevertheless, there is a scarcity of research on the effects of acupuncture treatment at GV14. This study investigated the effects of acupuncture at GV14 on cerebral blood flow (CBF), especially that in the basilar artery (BA) and the middle cerebral arteries (MCA). Sixteen healthy men aged 20 to 29 years were enrolled in this study. CBF velocity and cerebrovascular reactivity (CVR) were measured using transcranial Doppler sonography (TCD). The following were assessed: closed circuit rebreathing- (CCR-) induced carbon dioxide (CO2) reactivity, modified blood flow velocity at 40 mmHg (CV40) on BA and MCAs, blood pressure (BP), and heart rate (HR). Observed results were obtained after comparison with the baseline evaluation. Statistically significant elevations in CO2 reactivity were recorded in the BA (3.28 to 4.70, p < 0.001 ) and MCAs (right: 3.81 to 5.25, p = 0.001 ; left: 3.84 to 5.12, p = 0.005 ) after acupuncture at GV14. The CV40 increased statistically significantly only in the BA (45.49 to 50.41, p = 0.003 ). No change was observed in BP (106.83 to 107.08 (mmHg), p = 0.335 ) and HR (77 to 75 (bpm), p = 0.431 ). Acupuncture at GV14 improved CBF velocity. These results could be explained by the regulation of endothelium-dependent vessel dilation effected by acupuncture. This trial is registered with Korean Clinical Trial Registry (http://cris.nih.go.kr; registration number: KCT0004787).


2006 ◽  
Vol 290 (3) ◽  
pp. H1081-H1089 ◽  
Author(s):  
Jamila Ibrahim ◽  
Ann McGee ◽  
Delyth Graham ◽  
John C. McGrath ◽  
Anna F. Dominiczak

Cerebral blood flow (CBF) is maintained constant despite changes in systemic blood pressure (BP) through multiple mechanisms of autoregulation such as vascular myogenic reactivity. Our aim was to determine myogenic characteristics of cannulated middle cerebral arteries (MCA) in male and female stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) at 12 wk of age under pressurised no-flow conditions. MCA pressure-diameter relationships (20–200 mmHg) were constructed in active (with calcium) and passive (without calcium) conditions, and myogenic and mechanical properties were determined. Myogenic reactivity in WKY ( P < 0.05) and SHRSP ( P < 0.05) males was impaired compared with their female counterparts. Comparison of SHRSP with WKY in males revealed similar myogenic reactivity, but in females SHRSP exhibited augmented myogenic reactivity ( P < 0.05). In both sexes, myogenic tone yielded at lower pressure in SHRSP compared with WKY vessels (120–140 vs. 140–180 mmHg). Stress-strain relationships and elastic moduli in WKY rats showed that vessels were stiffer in females than in males. Conversely, in SHRSP, male vessels were stiffer than female vessels. Comparison of strains in males indicated that stiffness was increased in SHRSP compared with WKY vessels, whereas the converse was observed in females. These findings demonstrate that MCA myogenic and distensibility characteristics exhibit significant sex- and strain-dependent differences. Inappropriate myogenic adaptation and augmented vascular stiffness, particularly in male SHRSP, are potential limiting factors in blood flow autoregulation and may increase the predisposition for stroke-related cerebrovascular events.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
P Mason McClatchey

Introduction: Impaired tissue oxygenation is observed in many disease states including congestive heart failure, diabetes, cancer and aging. Decreased tissue perfusion and heterogeneous distribution of blood flow in the microvasculature contributes to this pathology. The physiological mechanisms regulating homogeneity/heterogeneity of microvascular perfusion are presently unknown. We hypothesized that microfluidic properties of the glycocalyx would promote perfusion homogeneity. Methods: To test our hypothesis, we used established empirical formulations for modelling blood viscosity in vivo (blood vessels) and in vitro (glass tubes). We first assess distribution of blood flow in idealized arteriolar networks. We next simulated distribution of blood flow at an idealized capillary bifurcation. Finally, we simulated velocity profiles and pressure gradients within the vessel lumen with varying glycocalyx properties using a computational fluid dynamics approach. Results: We found that transit time heterogeneity (as assessed by STD to mean ratio) was increased approximately 9x (6.9x-10.6x) using in vitro formulations of blood viscosity relative to in vivo formulations. This effect was mathematically accounted for by increased effective blood viscosity in smaller arterioles. We also found that distribution of blood flow at an idealized microvascular bifurcation was more symmetric using the in vivo formulation than the in vitro formulation (approximately 2x greater disparity between flow in downstream vessels). This effect was mathematically accounted for by an increased hematocrit dependence of blood viscosity. Both the diameter- and hematocrit-based changes in blood viscosity were entirely predictable from fluid dynamics simulations incorporating a space-filling, semi-permeable glycocalyx layer. Summary: Our simulations indicate that the mechanical properties of the endothelial glycocalyx promote homogeneous microvascular perfusion. Conclusions: The literature provides evidence of both glycocalyx degradation and impaired tissue perfusion in the same disease states. Preservation or restoration of normal glycocalyx properties may be a viable strategy for improving tissue perfusion in a wide variety of diseases.


2003 ◽  
Vol 95 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Antonio Rodríguez-Sinovas ◽  
Josep Bis ◽  
Inocencio Anivarro ◽  
Javier de la Torre ◽  
Antoni Bayés-Genís ◽  
...  

This study tested whether ischemia-reperfusion alters coronary smooth muscle reactivity to vasoconstrictor stimuli such as those elicited by an adventitial stimulation with methacholine. In vitro studies were performed to assess the reactivity of endothelium-denuded infarct-related coronary arteries to methacholine ( n = 18). In addition, the vasoconstrictor effects of adventitial application of methacholine to left anterior descending (LAD) coronary artery was assessed in vivo in pigs submitted to 2 h of LAD occlusion followed by reperfusion ( n = 12), LAD deendothelization ( n = 11), or a sham operation ( n = 6). Endothelial-dependent vasodilator capacity of infarct-related LAD was assessed by intracoronary injection of bradykinin ( n = 13). In vitro, smooth muscle reactivity to methacholine was unaffected by ischemia-reperfusion. In vivo, baseline methacholine administration induced a transient and reversible drop in coronary blood flow (9.6 ± 4.6 to 1.9 ± 2.6 ml/min, P < 0.01), accompanied by severe left ventricular dysfunction. After ischemia-reperfusion, methacholine induced a prolonged and severe coronary blood flow drop (9.7 ± 7.0 to 3.4 ± 3.9 ml/min), with a significant delay in recovery ( P < 0.001). Endothelial denudation mimics in part the effects of methacholine after ischemia-reperfusion, and intracoronary bradykinin confirmed the existence of endothelial dysfunction. Infarct-related epicardial coronary artery shows a delayed recovery after vasoconstrictor stimuli, because of appropriate smooth muscle reactivity and impairment of endothelial-dependent vasodilator capacity.


2012 ◽  
Vol 302 (6) ◽  
pp. H1330-H1339 ◽  
Author(s):  
Virginie Bolduc ◽  
Edward Baraghis ◽  
Natacha Duquette ◽  
Nathalie Thorin-Trescases ◽  
Jean Lambert ◽  
...  

Endothelial dysfunction and oxidative stress contribute to the atherosclerotic process that includes stiffening of large peripheral arteries. In contrast, our laboratory previously reported a paradoxical increase in cerebrovascular compliance in LDLr−/−:hApoB+/+ atherosclerotic (ATX) mice ( 7 ). We hypothesized that prevention of cerebral artery endothelial dysfunction with a chronic dietary antioxidant intake would normalize the changes in cerebral artery wall structure and biomechanics and prevent the decline in basal cerebral blood flow associated with atherosclerosis. Three-month-old ATX mice were treated, or not, for 3 mo with the polyphenol (+)-catechin (CAT; 30 mg·kg−1·day−1) and compared with wild-type controls. In isolated, pressurized cerebral arteries from ATX mice, CAT prevented endothelial dysfunction (deterioration of endothelium-dependent, flow-mediated dilations; P < 0.05), the inward hypertrophic structural remodeling (increase in the wall-to-lumen ratio; P < 0.05), and the rise in cerebrovascular compliance (rightward shift of the stress-strain curve measured in passive conditions, reflecting mechanical properties of the arterial wall; P < 0.05). Doppler optical coherence tomography imaging in vivo confirmed these findings, showing that cerebral compliance was higher in ATX mice and normalized by CAT ( P < 0.05). CAT also prevented basal cerebral hypoperfusion in ATX mice ( P < 0.05). Active remodeling of the cerebrovascular wall in ATX mice was further suggested by the increase ( P < 0.05) in pro-metalloproteinase-9 activity, which was normalized by CAT. We conclude that, by preserving the endothelial function, a chronic treatment with CAT prevents the deleterious effect of severe dyslipidemia on cerebral artery wall structure and biomechanical properties, contributing to preserving resting cerebral blood flow.


2018 ◽  
Vol 39 (8) ◽  
pp. 1570-1587 ◽  
Author(s):  
Christian Staehr ◽  
Lise Hangaard ◽  
Elena V Bouzinova ◽  
Sukhan Kim ◽  
Rajkumar Rajanathan ◽  
...  

Familial hemiplegic migraine type 2 (FHM2) is associated with inherited point-mutations in the Na,K-ATPase α2 isoform, including G301R mutation. We hypothesized that this mutation affects specific aspects of vascular function, and thus compared cerebral and systemic arteries from heterozygote mice bearing the G301R mutation (Atp1a2+/−G301R) with wild type (WT). Middle cerebral (MCA) and mesenteric small artery (MSA) function was compared in an isometric myograph. Cerebral blood flow was assessed with Laser speckle analysis. Intracellular Ca2+ and membrane potential were measured simultaneously. Protein expression was semi-quantified by immunohistochemistry. Protein phosphorylation was analysed by Western blot. MSA from Atp1a2+/−G301R and WT showed similar contractile responses. The Atp1a2+/−G301R MCA constricted stronger to U46619, endothelin and potassium compared to WT. This was associated with an increased depolarization, although the Ca2+ change was smaller than in WT. The enhanced constriction of Atp1a2+/−G301R MCA was associated with increased cSrc activation, stronger sensitization to [Ca2+]i and increased MYPT1 phosphorylation. These differences were abolished by cSrc inhibition. Atp1a2+/−G301R mice had reduced resting blood flow through MCA in comparison with WT mice . FHM2-associated mutation leads to elevated contractility of MCA due to sensitization of the contractile machinery to Ca2+, which is mediated via Na,K-ATPase/Src-kinase/MYPT1 signalling.


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