Abstract 357: Cerebral Arterial Endothelial Dysfunction in the Post-Cardiac Arrest Period

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Frederik B Hansen ◽  
Goncalo Esteves ◽  
Niels Secher ◽  
Bo Lofgren ◽  
Ulf Simonsen ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Endothelial Dysfunction ◽  
Cerebral Arteries ◽  
Channel Blockers ◽  
Sprague Dawley ◽  
No Donor ◽  
Sprague Dawley Rats ◽  
Middle Cerebral Arteries ◽  
Cerebral Vasodilation ◽  
Synthase Inhibitor

Introduction: Cardiac arrest (CA) has a poor prognosis due to brain injury that progresses over time. Endothelial dysfunction may play an important role in the impairment of the cerebral circulation after CA. Aims: To investigate 1) whether endothelial dysfunction is present in cerebral arteries, and 2) if the altered endothelial function is caused by increased activity of calcium-activated potassium (K ca ) channels. Methods: Male Sprague-Dawley rats (403g±24g) were anaesthetized, intubated and ventilated. Four groups were examined; two CA groups observed for either 2 hours (2h-CA, n=10) or 4 hours (4h-CA, n=10) and two corresponding sham groups (2h-sham, n=10; 4h-sham, n=10). Following 7 minutes of asphyxial CA, the rats were resuscitated using adrenaline, ventilation, and chest compressions. Middle cerebral arteries were isolated and examined in wire-myographs. Results: Cerebral vasodilation was significantly enhanced in response to bradykinin in arteries from 4h-CA rats when compared to 4h-sham rats (4h-sham: E max 58% (5.57 of 9.69) ± 6% vs 4h-CA: E max 84% (6.16 of 7.32) ± 4%, p=0.007). Likewise, vasodilation induced by NS309 (K Ca -channel activator) was increased in CA rats when compared to sham rats. In the presence of L-NAME (NO synthase inhibitor), bradykinin induced vasodilation was significantly augmented in 4h-CA rats when compared to 4h-sham rats, whereas SNP (NO donor) induced vasodilation was similar between groups. In the presence of L-NAME and K Ca -channel blockers (UCL1684 and ICA-17043), bradykinin induced vasodilation was abolished in cerebral arteries in all four groups. Conclusion: Our findings demonstrate an enhanced endothelial-dependent vasodilation in cerebral arteries in the post-cardiac arrest period. The increased vasodilatory response may be explained by increased endothelial K Ca -channel activity and bioavailability of NO, and may contribute to dysregulation of cerebral blood flow after CA.

Estrogen regulates myogenic tone in pressurized cerebral arteries by enhanced basal release of nitric oxide

1997 ◽  
Vol 273 (5) ◽  
pp. H2248-H2256 ◽  
Author(s):  
Peter Skarsgard ◽  
Cornelis Van Breemen ◽  
Ismail Laher
Keyword(s):  
Nitric Oxide ◽  
Cerebral Arteries ◽  
Calcium Ionophore ◽  
Myogenic Tone ◽  
Sprague Dawley ◽  
No Donor ◽  
Sprague Dawley Rats ◽  
Middle Cerebral Arteries ◽  
Basal Release ◽  
Endogenous Estrogen

Second-order middle cerebral arteries (135.0 ± 4.6 μm ID) from male, female, ovariectomized female (no endogenous estrogen), and estrogen-treated ovariectomized female Sprague-Dawley rats were harvested and mounted in a pressure myograph. Myogenic response was recorded over a pressure range of 10–100 mmHg and was repeated in the presence of N ω-nitro-l-arginine methyl ester (l-NAME; 2 × 10−4 M), an inhibitor of nitric oxide (NO) synthase, and after endothelium removal, to examine the contribution of NO to net myogenic tone. With intact endothelium, there were no differences in myogenic tone between the groups, but in the presence of l-NAME and after endothelium removal, estrogen-exposed vessels developed significantly greater tone at high transmural pressure. There were no differences in sensitivity to sodium nitroprusside, an NO donor, or A-23187, a calcium ionophore. These results suggest an increase in basal release of NO in cerebral arteries exposed to estrogen, without change in NO sensitivity or maximally stimulated NO release.

scholarly journals Angiotensin-(1-7) and low-dose angiotensin II infusion reverse salt-induced endothelial dysfunction via different mechanisms in rat middle cerebral arteries

2010 ◽  
Vol 299 (4) ◽  
pp. H1024-H1033 ◽  
Author(s):  
Matthew J. Durand ◽  
Gábor Raffai ◽  
Brian D. Weinberg ◽  
Julian H. Lombard
Keyword(s):  
Endothelial Dysfunction ◽  
Receptor Antagonist ◽  
Intravenous Infusion ◽  
Low Dose ◽  
Cerebral Arteries ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Mas Receptor ◽  
Middle Cerebral Arteries

The goals of this study were to 1) determine the acute effect of ANG-(1-7) on vascular tone in isolated middle cerebral arteries (MCAs) from Sprague-Dawley rats fed a normal salt (NS; 0.4% NaCl) diet, 2) evaluate the ability of chronic intravenous infusion of ANG-(1-7) (4 ng·kg−1·min−1) for 3 days to restore endothelium-dependent dilation to acetylcholine (ACh) in rats fed a high-salt (HS; 4% NaCl) diet, and 3) determine whether the amelioration of endothelial dysfunction by ANG-(1-7) infusion in rats fed a HS diet is different from the protective effect of low-dose ANG II infusion in salt-fed rats. MCAs from rats fed a NS diet dilated in response to exogenous ANG-(1-7) (10−10–10−5 M). Chronic ANG-(1-7) infusion significantly reduced vascular superoxide levels and restored the nitric oxide-dependent dilation to ACh (10−10–10−5 M) that was lost in MCAs of rats fed a HS diet. Acute vasodilation to ANG-(1-7) and the restoration of ACh-induced dilation by chronic ANG-(1-7) infusion in rats fed a HS diet were blocked by the Mas receptor antagonist [d-ALA( 7 )]-ANG-(1-7) or the ANG II type 2 receptor antagonist PD-123319 and unaffected by ANG II type 1 receptor blockade with losartan. The restoration of ACh-induced dilation in MCAs of HS-fed rats by chronic intravenous infusion of ANG II (5 ng·kg−1·min−1) was blocked by losartan and unaffected by d-ALA. These findings demonstrate that circulating ANG-(1-7), working via the Mas receptor, restores endothelium-dependent vasodilation in cerebral resistance arteries of animals fed a HS diet via mechanisms distinct from those activated by low-dose ANG II infusion.

scholarly journals Angiogenesis after Stroke is Correlated with Increased Numbers of Macrophages: The Clean-up Hypothesis

2001 ◽  
Vol 21 (10) ◽  
pp. 1223-1231 ◽  
Author(s):  
Panya S. Manoonkitiwongsa ◽  
Catherine Jackson-Friedman ◽  
Paul J. McMillan ◽  
Robert L. Schultz ◽  
Patrick D. Lyden
Keyword(s):  
Microvessel Density ◽  
Focal Cerebral Ischemia ◽  
Cerebral Arteries ◽  
Sprague Dawley ◽  
Regional Cerebral Blood ◽  
Ischemic Brain ◽  
Sprague Dawley Rats ◽  
Middle Cerebral Arteries ◽  
The Brain ◽  
Left Middle

Brain cells manufacture and secrete angiogenic peptides after focal cerebral ischemia, but the purpose of this angiogenic response is unknown. Because the maximum possible regional cerebral blood flow is determined by the quantity of microvessels in each unit volume, it is possible that angiogenic peptides are secreted to generate new collateral channels; other possibilities include neuroprotection, recovery/regeneration, and removal of necrotic debris. If the brain attempts to create new collaterals, microvessel density should increase significantly after ischemia. Conversely, if angiogenic-signaling molecules serve some other purpose, microvessel densities may increase slightly or not at all. To clarify, the authors measured microvessel densities with quantitative morphometry. Left middle cerebral arteries of adult male Sprague–Dawley rats were occluded with intraluminal nylon suture for 4 hours followed by 7, 14, 19, or 30 days of reperfusion. Controls received no surgery or suture occlusion. Changes in microvessel density and macrophage numbers were measured by light microscopic morphometry using semiautomated stereologic methods. Microvessel density increased only in the ischemic margin adjacent to areas of pannecrosis and was always associated with increased numbers of macrophages. Ischemic brain areas without macrophages displayed no vascularity changes compared with normal animals. These data suggest that ischemia-induced microvessels are formed to facilitate macrophage infiltration and removal of necrotic brain.

scholarly journals Effect of Nearby Construction Activity on Endothelial Function, Sensitivity to Nitric Oxide, and Potassium Channel Activity in the Middle Cerebral Arteries of Rats

2020 ◽  
Author(s):  
Maia N Terashvili ◽  
Kaleigh N Kozak ◽  
Debebe Gebremedhin ◽  
Linda A Allen ◽  
Alison L Gifford ◽  
...  
Keyword(s):  
Single Channel ◽  
Cerebral Arteries ◽  
High Sensitivity ◽  
Vibration Monitoring ◽  
Raspberry Pi ◽  
Sprague Dawley ◽  
Film Sensor ◽  
No Donor ◽  
Middle Cerebral Arteries ◽  
Construction Activity

The present study assessed the effect of nearby construction activity on the responses of rat middle cerebral arteries (MCA)to the endothelium-dependent vasodilator acetylcholine and the NO donor sodium nitroprusside (SNP) and the activity of MaxiK potassium channels in MCA smooth muscle cells from male Sprague–Dawley rats. Two monitoring systems were used to assess vibrations in the animal rooms during and immediately after construction activities near the research building where the animal facility is located. One was a commercially available system; the other was a Raspberry-Pi (RPi)–based vibration monitoring system designed in our laboratory that included a small computing unit attached to a rolling sensor (low sensitivity) and a piezoelectric film sensor (high sensitivity). Both systems recorded increased levels of vibration during construction activity outside the building. During the construction period, vasodilator responses to acetylcholine and SNP were abolished, and MaxiK single-channel current opening frequency and open-state probability in cell-attached patches of isolated MCA myocytes were dramatically decreased. Recovery of acetylcholine- and SNP-induced dilation was minimal in MCA from rats studied after completion of construction but housed in the animal facility during construction, whereas responses to acetylcholine and SNP were intact in rats purchased, housed, and studied after construction. Baseline levels of vibration returned after the completion of construction, concomitant with the recovery of normal endothelium-dependent vasodilation to acetylcholine and of NO sensitivity assessed by using SNP in MCA from animals obtained after construction. The results of this study indicate that the vibration associated with nearby construction can have highly disruptive effects on crucial physiologic phenotypes.

Membrane hyperpolarization is a mechanism of endothelium-dependent cerebral vasodilation

1990 ◽  
Vol 259 (3) ◽  
pp. H668-H673 ◽  
Author(s):  
J. E. Brayden
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Potassium Channel ◽  
Cerebral Arteries ◽  
Channel Blockers ◽  
Membrane Hyperpolarization ◽  
Middle Cerebral Arteries ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Cerebral Vasodilation

Acetylcholine (ACh)-induced hyperpolarization of cerebral arteries requires a functional endothelium. The hyperpolarization is reversed by potassium-channel blockers. The goal of this study was to determine whether the hyperpolarization is causally related to endothelium-dependent dilation of isolated cerebral arteries. ACh hyperpolarized rabbit middle cerebral arteries by up to 19 mV. The hyperpolarizations were sustained and did not occur in arteries without endothelial cells or in the presence of potassium-channel inhibitors (3 x 10(-6) M glibenclamide or 5 x 10(-5) M BaCl2). ACh-induced dilator responses were inhibited but not abolished by glibenclamide or BaCl2. Methylene blue also inhibited the dilator responses, and a combination of glibenclamide or BaCl2 and methylene blue greatly diminished the dilation. Nitric oxide relaxed but did not hyperpolarize the vascular smooth muscle cells, and BaCl2 had no effect on the nitric oxide-induced relaxations. These data indicate that the overall cerebral arterial dilator response to ACh is determined by the combined effects of membrane hyperpolarization, which closes voltage-dependent calcium channels, and the actions of a second endothelial factor, probably endothelium-derived relaxing factor.

scholarly journals In vivo regulation of renal expression of (pro)renin receptor by a low-sodium diet

2012 ◽  
Vol 303 (12) ◽  
pp. F1652-F1657 ◽  
Author(s):  
Luis C. Matavelli ◽  
Jiqian Huang ◽  
Helmy M. Siragy
Keyword(s):  
Signaling Pathway ◽  
Urinary Sodium Excretion ◽  
Sprague Dawley ◽  
No Donor ◽  
Low Sodium Diet ◽  
Sprague Dawley Rats ◽  
Cgmp Analog ◽  
Synthase Inhibitor ◽  
Renal Expression

Effects of low salt (LS) on (pro)renin receptor (PRR) expression are not well established. We hypothesized that LS enhances renal PRR expression via the cGMP-protein kinase G (PKG) signaling pathway. Sprague-Dawley rats were fed a normal-salt (NS) or LS diet associated with intrarenal cortical administration of vehicle (V), the nitric oxide (NO) synthase inhibitor nitro-l-arginine methyl ester (l-NAME), the NO donor S-nitroso- N-acetyl-dl-penicillamine (SNAP), the cGMP analog 8-bromoguanosine (8-Br)-cGMP, the guanylyl cyclase inhibitor 1H-[1, 2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), or a PKG inhibitor (PKGi) for 6 days via osmotic minipump. We evaluated the effects of each treatment on renal interstitial fluid (RIF) levels of nitrate/nitrite and cGMP and renal PRR expression. There were no significant changes in blood pressure with any of the treatments. Urinary sodium excretion was significantly lower in rats given a LS diet. Compared with NS + V, RIF nitrate/nitrite and cGMP levels increased in LS + V rats. In NS groups, RIF nitrate/nitrite and cGMP levels did not change with l-NAME, ODQ, or PKGi and increased in response to SNAP. 8-Br-cGMP increased RIF cGMP but not RIF nitrate/nitrite. In LS groups, RIF nitrate/nitrite decreased with l-NAME and did not change with ODQ or PKGi whereas RIF cGMP decreased with l-NAME, ODQ, and PKGi. PRR mRNA and protein increased in LS + V. In NS rats, PRR mRNA and protein increased in response to 8-Br-GMP and were not affected by any of other treatments. In LS rats, PRR mRNA and protein decreased significantly in response to l-NAME, ODQ, and PKGi. We conclude that LS intake enhances renal expression of PRR via cGMP-PKG signaling pathway.

Angiotensin II type 1 receptor is involved in flow-induced vasomotor responses of isolated middle cerebral arteries. Role of oxidative stress

2021 ◽  
Author(s):  
Ivana Jukic ◽  
Zrinka Mihaljevic ◽  
Anita Matic ◽  
Martina Mihalj ◽  
Natasa Kozina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Arteries ◽  
Control Group ◽  
Ros Production ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Middle Cerebral Arteries ◽  
Losartan Group

This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague-Dawley rats. Eleven-weeks old, healthy male Sprague-Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilations was compared to control group. Nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) and cyclooxygenase inhibitor indomethacin (INDO) significantly reduced FID in control group. The attenuated FID in losartan group was further reduced by INDO only at ∆100 mmHg, whereas L-NAME had no effect. In losartan group, TEMPOL (a superoxide scavenger) restored dilatation, while TEMPOL+L-NAME together significantly reduced FID compared to restored dilatation with TEMPOL alone. Direct fluorescence measurements of NO and reactive oxygen species (ROS) production in MCA, in no-flow conditions revealed significantly reduced vascular NO levels with AT1R blockade compared to control group, while flow increased the NO and ROS production in losartan group and had no effect in control group. In losartan group, TEMPOL decreased ROS production in both no-flow and flow conditions. AT1R blockade elicited increased serum concentrations of AngII, 8-iso-PGF2α, and TBARS, and decreased antioxidant enzyme activity (SOD and CAT). These results suggest that in small isolated cerebral arteries: 1) AT1 receptor maintains dilations in physiological conditions; 2) AT1R blockade leads to increased vascular and systemic oxidative stress, which underlies impaired FID.

Interaction of myogenic mechanisms and hypoxic dilation in rat middle cerebral arteries

2002 ◽  
Vol 283 (6) ◽  
pp. H2276-H2281 ◽  
Author(s):  
Yanping Liu ◽  
David R. Harder ◽  
Julian H. Lombard
Keyword(s):  
Transmembrane Potential ◽  
Cerebral Arteries ◽  
Vessel Diameter ◽  
Transmural Pressure ◽  
Sprague Dawley ◽  
Pressure Elevation ◽  
Sprague Dawley Rats ◽  
Middle Cerebral Arteries ◽  
Arterial Dilation ◽  
Myogenic Responses

The goal of this study was to determine how myogenic responses and vascular responses to reduced Po 2 interact to determine vascular smooth muscle (VSM) transmembrane potential and active tone in isolated middle cerebral arteries from Sprague-Dawley rats. Stepwise elevation of transmural pressure led to depolarization of the VSM cells and myogenic constriction, and reduction of the O2concentration of the perfusion and superfusion reservoirs from 21% O2 to 0% O2 caused vasodilation and VSM hyperpolarization. Myogenic constriction and VSM depolarization in response to transmural pressure elevation still occurred at reduced Po 2. Arterial dilation in response to reduced Po 2 was not impaired by pressure elevation but was significantly reduced at the lowest transmural pressure (60 mmHg). However, the magnitude of VSM hyperpolarization was unaffected by transmural pressure elevation. This study demonstrates that myogenic activation in response to transmural pressure elevation does not override hypoxic relaxation of middle cerebral arteries and that myogenic responses and hypoxic relaxation can independently regulate vessel diameter despite substantial changes in the other variable.

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