Effect of age on the vascular proteome in middle cerebral arteries and mesenteric resistance arteries in mice

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.

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Development of fetal vascular responses to endothelin-1 and acetylcholine in the sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.280.2.r554 ◽

2001 ◽

Vol 280 (2) ◽

pp. R554-R562 ◽

Cited By ~ 30

Author(s):

Cheryl C. Docherty ◽

Judit Kalmar-Nagy ◽

Marc Engelen ◽

Peter W. Nathanielsz

Keyword(s):

Cerebral Arteries ◽

Renal Arteries ◽

Resistance Arteries ◽

Endothelin 1 ◽

Vascular Bed ◽

Developmental Age ◽

Middle Cerebral Arteries ◽

Blood Flow Control ◽

Critical Developmental Period ◽

Systemic Arteries

Responses to K+, endothelin-1 (ET-1), and acetylcholine (ACh) of isolated adrenal, femoral, middle cerebral, and renal arteries from fetal [110–145 days gestational age (dGA, term ∼148 dGA)] and 0- to 24-h newborn (NB) lambs were evaluated using the technique of wire myography. Responses at distinct developmental ages for each vascular bed were compared. In all arteries sensitivity to K+-induced vasoconstriction was similar at all fetal age points examined. In contrast, sensitivity to ET-1 increased with increasing fetal age in arteries from all vascular beds. The magnitude of the maximal vasoconstriction was positively correlated with GA for K+in adrenal, femoral, and cerebral arteries and for ET-1 in femoral, cerebral, and renal arteries. Cerebral arteries showed a greater sensitivity when compared with the other systemic arteries to K+ and ET-1 at all fetal ages and to K+ in NB. ACh evoked relaxatory responses in fetal and NB femoral and adrenal arteries. However, renal arteries relaxed comparatively less in response to ACh, and no vasodilation was noted in middle cerebral arteries at any age points examined. For femoral arteries ACh-induced vasorelaxation decreased with increasing GA but was restored in arteries from NB lambs. In summary, the responsiveness of isolated resistance arteries varies with developmental age in the fetal and perinatal sheep and these effects are both agonist and vascular bed specific. The augmented sensitivity in response to ET-1 of middle cerebral compared with other systemic arteries may reflect the importance of cerebral blood flow control during this critical developmental period.

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Can Myogenic Tone Protect Endothelial Function? Integrating Myogenic Activation and Dilator Reactivity for Cerebral Resistance Arteries in Metabolic Disease

Journal of Vascular Research ◽

10.1159/000516088 ◽

2021 ◽

pp. 1-15

Author(s):

Brayden D. Halvorson ◽

John J. McGuire ◽

Krishna K. Singh ◽

Joshua T. Butcher ◽

Julian H. Lombard ◽

...

Keyword(s):

Endothelial Function ◽

Group Treatment ◽

Vascular Function ◽

Cerebral Arteries ◽

Resistance Arteries ◽

Multiple Risk Factors ◽

Cerebrovascular Function ◽

Obese Zucker Rat ◽

Middle Cerebral Arteries ◽

Slope Treatment

The obese Zucker rat (OZR) manifests multiple risk factors for impaired cerebrovascular function, including hypertension and insulin resistance although how they combine to produce integrated vascular function is unclear. As studies have suggested that myogenic activation (MA) severity for middle cerebral arteries (MCAs) may be proportional to hypertension severity, we hypothesized that MA will negatively correlate with dilator reactivity in OZR. MA of MCA from OZR was divided into low, medium, and high based on the slope of MA, while MCA reactivity and vascular metabolite bioavailability were assessed in all groups. Endothelium-dependent dilation of MCA in OZR was attenuated and correlated with the MA slope. Treatment of OZR MCA with TEMPOL (antioxidant) improved dilation in low or medium MA groups, but had less impact on high MA. Alternatively, treatment with gadolinium to normalize MA in OZR had reduced impact on dilator reactivity in MCA from low and medium MA groups, but improved responses in the high group. Treatment with both agents resulted in dilator responses that were comparable across all groups. These results suggest that, under conditions with stronger MA, endothelial function may receive some protection despite the environment, potentially from the ability of MCA to reduce wall tension despite increased pressure.

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Restoration of Endothelial Function inPparα−/−Mice by Tempol

PPAR Research ◽

10.1155/2015/728494 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Neerupma Silswal ◽

Nikhil Parelkar ◽

Jon Andresen ◽

Michael J. Wacker

Keyword(s):

Endothelial Function ◽

Cerebral Arteries ◽

Lipoprotein Metabolism ◽

Vascular Wall ◽

Nuclear Hormone Receptor ◽

Peroxisome Proliferator ◽

Resistance Arteries ◽

Peroxisome Proliferator Activated Receptor ◽

Middle Cerebral Arteries ◽

Ros Scavenger

Peroxisome proliferator activated receptor alpha (PPARα) is one of the PPAR isoforms belonging to the nuclear hormone receptor superfamily that regulates genes involved in lipid and lipoprotein metabolism. PPARαis present in the vascular wall and is thought to be involved in protection against vascular disease. To determine if PPARαcontributes to endothelial function, conduit and cerebral resistance arteries were studied inPparα−/−mice using isometric and isobaric tension myography, respectively. Aortic contractions to PGF2αand constriction of middle cerebral arteries to phenylephrine were not different between wild type (WT) andPparα−/−; however, relaxation/dilation to acetylcholine (ACh) was impaired. There was no difference in relaxation between WT andPparα−/−aorta to treatment with a nitric oxide (NO) surrogate indicating impairment in endothelial function. Endothelial NO levels as well as NO synthase expression were reduced inPparα−/−aortas, while superoxide levels were elevated. Two-week feeding with the reactive oxygen species (ROS) scavenger, tempol, normalized ROS levels and rescued the impaired endothelium-mediated relaxation inPparα−/−mice. These results suggest thatPparα−/−mice have impaired endothelial function caused by decreased NO bioavailability. Therefore, activation of PPARαreceptors may be a therapeutic target for maintaining endothelial function and protection against cardiovascular disease.

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Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00605.2001 ◽

2002 ◽

Vol 283 (6) ◽

pp. H2177-H2186 ◽

Cited By ~ 39

Author(s):

Guy Lagaud ◽

Venkateswarlu Karicheti ◽

Harm. J. Knot ◽

George J. Christ ◽

Ismail Laher

Keyword(s):

Membrane Potential ◽

Gap Junctions ◽

Cerebral Arteries ◽

Myogenic Tone ◽

Detectable Effect ◽

Resistance Arteries ◽

Potential Oscillations ◽

Gap Junction Communication ◽

Middle Cerebral Arteries ◽

Isolated Arteries

The effects of two structurally distinct inhibitors of gap junction communication were studied by using three different forms of vasoconstriction in pressurized rat middle cerebral arteries. The sensitivity of myogenic tone (at 60 mmHg), vasopressin-induced tone (10 nM, at 20 mmHg), and depolarizing solution-induced tone (80 mM K+, at 20 mmHg) to inhibition by heptanol (1.0 μM to 3.0 mM) or 18α-glycyrrhetinic acid (18α-GA, 1.0 to 50 μM) were determined. Pressure-induced myogenic tone was inhibited by heptanol (IC50 = 0.75 ± 0.09 mM) and 18α-GA (∼30 μM). Vasopressin-induced vasoconstriction was also inhibited by heptanol (IC50= 0.4 ± 0.3 mM) and 18α-GA (>1 μM). Depolarizing solution-induced vasoconstriction was less sensitive to inhibition by heptanol compared to vasopressin ( P < 0.01) or pressure-induced constriction ( P < 0.05). However, 18α-GA did not inhibit depolarization-induced constriction. Sharp microelectrode experiments on isolated arteries revealed stable membrane potentials, with no detectable effect of heptanol (1 mM) or 18α-GA (20–30 μM) on the average membrane potential at 20 mmHg. However, ≈20% of impaled cells (5 of 28) exhibited uncharacteristic oscillations in membrane potential after pharmacological uncoupling. At 60 mmHg a ≈7- to 9-mV hyperpolarization and corresponding vasodilation (≈50%) was observed, and the frequency of membrane potential oscillations doubled (9 of 23 cells). These data indicate that gap junctions play an important role in the maintenance and modulation of membrane potential and tone in cerebral resistance arteries.

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DIFFICULTIES IN DIAGNOSING MOYA-MOYA DISEASE (CLINICAL CASE)

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2020-22-10-48-53 ◽

2020 ◽

pp. 48-53

Author(s):

Novikova I.N. ◽

Popova T.F. ◽

Gribacheva I.A. ◽

Petrova E.V. ◽

Marushchak A.A. ◽

...

Keyword(s):

Cerebral Angiography ◽

Neurological Disorders ◽

Clinical Case ◽

Carotid Arteries ◽

Internal Carotid ◽

Cerebral Arteries ◽

Moya Moya Disease ◽

Middle Cerebral Arteries ◽

Internal Carotid Arteries ◽

Made In

Moya-Moya disease is a rare progressive chronic cer-ebrovascular disease characterized by a narrowing of the lumen of the intracranial segments of the internal carotid arteries, as well as the initial segments of the anterior and middle cerebral arteries with the devel-opment of a network of small vascular anastomoses. Violations of blood supply due to occlusion lead to the development of ischemic strokes in the correspond-ing pools, and ruptures of vascular anastomoses - to the development of hemorrhagic strokes, causing a variety of neurological disorders. The article presents a clinical case of Moya-Moya disease in a 31-year-old patient. The disease was manifested by acute disorders of cerebral circulation in ischemic and hemorrhagic types. The diagnosis was made in accordance with the diagnostic criteria of the disease based on the data of endovascular cerebral angiography.

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Nonspecificity of increased density of middle cerebral arteries as a sign of infarction

American Journal of Roentgenology ◽

10.2214/ajr.151.5.1058-a ◽

1988 ◽

Vol 151 (5) ◽

pp. 1058-1058

Author(s):

CH McIver

Keyword(s):

Cerebral Arteries ◽

Middle Cerebral Arteries

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Modulation of cerebral arterial tone by endothelium-derived relaxing factor

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.264.4.h1245 ◽

1993 ◽

Vol 264 (4) ◽

pp. H1245-H1250 ◽

Cited By ~ 1

Author(s):

J. E. Brian ◽

R. H. Kennedy

Keyword(s):

Nitric Oxide ◽

Muscle Tone ◽

Cerebral Arteries ◽

Maximum Tension ◽

Relaxing Factor ◽

Middle Cerebral Arteries ◽

Endothelium Derived Relaxing Factor ◽

Vascular Smooth Muscle Tone ◽

Dose Dependent ◽

Arterial Tone

This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro-L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT.

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Cerebral Hemodynamics and Intracranial Compliance Impairment in Critically Ill COVID-19 Patients: A Pilot Study

Brain Sciences ◽

10.3390/brainsci11070874 ◽

2021 ◽

Vol 11 (7) ◽

pp. 874

Author(s):

Sérgio Brasil ◽

Fabio Silvio Taccone ◽

Sâmia Yasin Wahys ◽

Bruno Martins Tomazini ◽

Filippo Annoni ◽

...

Keyword(s):

Critically Ill ◽

Cerebral Arteries ◽

Receiver Operating Curve ◽

Severe Illness ◽

Mean Flow ◽

Non Invasive ◽

Intracranial Compliance ◽

Middle Cerebral Arteries ◽

Primary Composite Outcome ◽

Cerebrovascular Hemodynamics

Introduction: One of the possible mechanisms by which the new coronavirus (SARS-Cov2) could induce brain damage is the impairment of cerebrovascular hemodynamics (CVH) and intracranial compliance (ICC) due to the elevation of intracranial pressure (ICP). The main objective of this study was to assess the presence of CVH and ICC alterations in patients with COVID-19 and evaluate their association with short-term clinical outcomes. Methods: Fifty consecutive critically ill COVID-19 patients were studied with transcranial Doppler (TCD) and non-invasive monitoring of ICC. Subjects were included upon ICU admission; CVH was evaluated using mean flow velocities in the middle cerebral arteries (mCBFV), pulsatility index (PI), and estimated cerebral perfusion pressure (eCPP), while ICC was assessed by using the P2/P1 ratio of the non-invasive ICP curve. A CVH/ICC score was computed using all these variables. The primary composite outcome was unsuccessful in weaning from respiratory support or death on day 7 (defined as UO). Results: At the first assessment (n = 50), only the P2/P1 ratio (median 1.20 [IQRs 1.00–1.28] vs. 1.00 [0.88–1.16]; p = 0.03) and eICP (14 [11–25] vs. 11 [7–15] mmHg; p = 0.01) were significantly higher among patients with an unfavorable outcome (UO) than others. Patients with UO had a significantly higher CVH/ICC score (9 [8–12] vs. 6 [5–7]; p < 0.001) than those with a favorable outcome; the area under the receiver operating curve (AUROC) for CVH/ICC score to predict UO was 0.86 (95% CIs 0.75–0.97); a score > 8.5 had 63 (46–77)% sensitivity and 87 (62–97)% specificity to predict UO. For those patients undergoing a second assessment (n = 29), after a median of 11 (5–31) days, all measured variables were similar between the two time-points. No differences in the measured variables between ICU non-survivors (n = 30) and survivors were observed. Conclusions: ICC impairment and CVH disturbances are often present in COVID-19 severe illness and could accurately predict an early poor outcome.

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