scholarly journals Amylin: Localization, Effects on Cerebral Arteries and on Local Cerebral Blood Flow in the Cat

2001 ◽  
Vol 1 ◽  
pp. 168-180 ◽  
Author(s):  
Lars Edvinsson ◽  
Peter J. Goadsby ◽  
Rolf Uddman
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Vessels ◽  
Cerebral Arteries ◽  
In Vivo Studies ◽  
Cerebral Blood Vessels ◽  
Local Cerebral Blood Flow ◽  
Doppler Flowmetry

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.

Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S198-S198
Author(s):  
Joseph R Meno ◽  
Thien-son K Nguyen ◽  
Elise M Jensen ◽  
G Alexander West ◽  
Leonid Groysman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Activation ◽  
In Vivo Studies ◽  
Blood Flow Response ◽  
Flow Response

The role of adenosine in hypercarbic hyperemia: in vivo and in vitro studies in adenosine 2A receptor knockout and wild-type mice

2009 ◽  
Vol 110 (5) ◽  
pp. 981-988 ◽  
Author(s):  
Grzegorz Miekisiak ◽  
Kristen Yoo ◽  
Adam L. Sandler ◽  
Tobias B. Kulik ◽  
Jiang-Fan Chen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Knockout Mice ◽  
Average Diameter ◽  
In Vitro Studies ◽  
Wild Type ◽  
Doppler Flowmetry ◽  
In The Wild

Object The authors tested the hypothesis that adenosine, acting through the A2A receptor, is not involved in hypercarbic hyperemia by assessing the effects of increased PaCO2 on cerebral blood flow (CBF) in vivo in wild-type and A2A receptor knockout mice. In addition, they evaluated the effect of abluminal pH changes in vitro on the diameter of isolated perfused penetrating arterioles harvested from wild-type and A2A receptor knockout mice. Methods The authors evaluated in a blinded fashion the CBF response during transient (60-second) hypercapnic (7% CO2) hypercarbia in anesthetized, ventilated C57Bl/6 wild-type and adenosine A2A receptor knockout mice. They also evaluated the hypercarbic response in the absence and presence of the nonselective and selective adenosine antagonists. Results Cerebral blood flow was measured using laser Doppler flowmetry. There were no differences between the CBF responses to hypercarbia in the wild-type and the knockout mice. Moreover, the hypercarbic hyperemia response was not affected by the adenosine receptor antagonists. The authors also tested the response to alteration in abluminal pH in isolated perfused, pressurized, penetrating arterioles (average diameter 63.3 ± 3.6 μm) harvested from wild-type (6 mice) and knockout (5 mice) animals. Arteriolar dilation in response to a decrease in abluminal pH, simulating the change in vivo during hypercarbia, was similar in wild-type (15.9 ± 2.6%) and A2A receptor knockout (17.7 ± 1.3%) mice. With abluminal application of CGS 21680 (10−6 M), an A2A receptor agonist, wild-type arterioles dilated in an expected manner (9.8 ± 0.7%), whereas A2A receptor knockout vessels had minimal response. Conclusions The results of the in vivo and in vitro studies in wild-type and A2A receptor knockout mice support the authors' hypothesis that hypercarbic vasodilation does not involve an adenosine A2A receptor–related mechanism.

scholarly journals Erythrocyte Extracts Enhance Neurogenic Vasoconstriction of Dog Cerebral Arteries in vitro

1984 ◽  
Vol 4 (3) ◽  
pp. 474-476 ◽  
Author(s):  
Tony J.-F. Lee ◽  
Michael P. McIlhany ◽  
Susan Sarwinski
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Blood Vessels ◽  
Cerebral Vasospasm ◽  
Cerebral Arteries ◽  
Cerebral Blood Vessels ◽  
Neurogenic Vasoconstriction ◽  
To Receive ◽  
Neurogenic Vasodilation

Cerebral blood vessels of the dog have been shown to receive vasodilator and constrictor nerves. In isolated ring arterial preparations, neurogenic vasodilation was blocked while neurogenic vasoconstriction was potentiated by hemolysates isolated from hemolyzed erythrocytes. These results suggest that an overall increase in cerebral neurogenic vasoconstriction may occur in vivo following subarachnoid hemorrhage. The significance of this finding in the pathogenesis of cerebral vasospasm is discussed.

Abstract WP498: Impaired Pericyte Constriction and Cerebral Blood Flow Autoregulationin Diabetes

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yedan Liu ◽  
Shaoxun Wang ◽  
Ya Guo ◽  
Huawei Zhang ◽  
Richard Roman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ex Vivo ◽  
Mitochondrial Dynamics ◽  
Vascular Cognitive Impairment ◽  
Treated Group ◽  
Diabetic Rats ◽  
Cerebrovascular Function

Diabetes is the primary pathological factor attributed to Alzheimer’s disease and vascular cognitive impairment. Previous studies demonstrated that hyperglycemia promoted oxidative stress in the cerebral vasculature. Cerebrovascular pericytes contribute to maintaining blood-brain barrier (BBB) integrity and regulating cerebral blood flow (CBF). However, whether hyperglycemia diminishes the contractile capability of pericytes, impairs CBF autoregulation and increases BBB permeability are unclear. In the present study, we examined the role of pericytes in cerebrovascular function and cognition in diabetes using cell culture in vitro , isolated penetrating arterioles ex vivo and CBF autoregulation in vivo . Reactive oxygen species were elevated in high glucose (HG, 30 mM) treated vs. normal glucose (NG, 5.5 mM) treated pericytes. Further, mitochondrial superoxide production was increased in HG-treated vs. NG-treated group (13.24 ± 1.01 arbitrary unit (a.u.)/30min vs. 6.98 ± 0.36 a.u./30min). Mitochondrial respiration decreased in HG-treated vs. NG-treated pericytes (3718 ± 185.9 pmol/min/mg, n=10 vs. 4742 ± 284.5 pmol/min/mg, n=10) as measured by a Seahorse XFe24 analyzer. HG-treated pericytes displayed fragmented mitochondria in association with increased fission protein (DRP1) and decreased fusion protein (OPA1) expression. HG-treated pericytes displayed lower contractile capability than NG-treated cells (20.23 ± 7.15% vs. 29.46 ± 9.41%). The myogenic response was impaired in penetrating arterioles isolated from diabetic rats in comparison with non-diabetic rats. Autoregulation of CBF measured by a laser Doppler flowmeter was impaired in diabetic rats compared with non-diabetic rats. Diabetic rats exhibited greater BBB leakage than control rats. The cognitive function was examined using an eight-arm water maze. Diabetic rats took longer time to escape than the non-diabetic rats indicating learning and memory deficits. In conclusion, hyperglycemia induces pericyte dysfunction by altering mitochondrial dynamics and diminishing contractile capability, which promotes BBB leakage, decreases CBF autoregulation and contributes to diabetes-related dementia.

scholarly journals In vitro and in vivo evaluation of hypothermia on pharmacokinetics and pharmacodynamics of nimodipine in rabbits

2017 ◽  
Vol 46 (1) ◽  
pp. 335-347 ◽  
Author(s):  
Yu-xing Fei ◽  
Tian-hong Zhang ◽  
Jing Zhao ◽  
He Ren ◽  
Ya-nan Du ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Protein Binding ◽  
Plasma Concentrations ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
Pharmacokinetics And Pharmacodynamics ◽  
In Vivo Evaluation

Objective To investigate the effect of hypothermia on the pharmacokinetics and pharmacodynamics of nimodipine in rabbits using in vivo and in vitro methods. Methods Five healthy New Zealand rabbits received a single dose of nimodipine (0.5 mg/kg) intravenously under normothermic and hypothermic conditions. Doppler ultrasound was used to monitor cerebral blood flow, vascular resistance, and heart rate. In vitro evaluations of protein binding, hepatocyte uptake and intrinsic clearance of liver microsomes at different temperatures were also conducted. Results Plasma concentrations of nimodipine were significantly higher in hypothermia than in normothermia. Nimodipine improved cerebral blood flow under both conditions, but had a longer effective duration during the hypothermic period. Low temperature decreased the intrinsic clearance of liver microsomes, with no change in protein binding or hepatocyte uptake of nimodipine. Conclusion Nimodipine is eliminated at a slower rate during hypothermia than during normothermia, mainly due to the decreased activity of cytochrome P450 enzymes. This results in elevated system exposure with little enhancement in pharmacological effect.

scholarly journals Catechin prevents severe dyslipidemia-associated changes in wall biomechanics of cerebral arteries in LDLr−/−:hApoB+/+ mice and improves cerebral blood flow

2012 ◽  
Vol 302 (6) ◽  
pp. H1330-H1339 ◽  
Author(s):  
Virginie Bolduc ◽  
Edward Baraghis ◽  
Natacha Duquette ◽  
Nathalie Thorin-Trescases ◽  
Jean Lambert ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Endothelial Dysfunction ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Strain Curve ◽  
Cerebral Hypoperfusion ◽  
Wall Structure ◽  
Artery Wall

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.

scholarly journals Role of the angiotensin II system in regulation of ovulation and blood flow in the rat ovary

Reproduction ◽  
2003 ◽  
pp. 425-435 ◽  
Author(s):  
K Mitsube ◽  
M Mikuni ◽  
M Matousek ◽  
U Zackrisson ◽  
M Brannstrom
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Angiotensin Ii Receptor ◽  
Doppler Flowmetry ◽  
Angiotensin Ii Receptor Subtypes ◽  
Specific Antagonist

The aim of the present study was to examine the roles of the angiotensin II receptor subtypes, AT(1) and AT(2), in ovulation, and to evaluate the contribution of angiotensin II-mediated pathways in regulation of ovarian blood flow. The AT(1)-specific antagonist, losartan, was administered alone or in combination with the AT(2)-specific antagonist, PD123319, to preovulatory rat ovaries perfused in vitro. Losartan (100 micromol l(-1)) did not affect the number of ovulations, whereas the combination of losartan (100 micromol l(-1)) and PD123319 (10 micromol l(-1)) inhibited ovulation. The angiotensin II antagonists did not affect the ovarian production of oestradiol, progesterone, prostaglandin E(2) (PGE(2)), PGF(2 alpha) or plasminogen activator activity. Ovarian nitric oxide production was inhibited by losartan. Ovarian blood flow was measured by laser Doppler flowmetry in vivo in preovulatory rat ovaries. Intrabursal injection of angiotensin II reduced ovarian blood flow of gonadotrophin-stimulated rats. Losartan had no effect on basal ovarian blood flow but completely blocked the angiotensin II-induced reduction. In contrast, treatment with PD123319 increased basal ovarian blood flow and failed to reverse the effect of exogenously administered angiotensin II, indicating that under physiological conditions, ovarian blood flow of the rat is negatively regulated by angiotensin II mainly through the action of AT(2). Taken together, these results indicate that two different types of angiotensin II receptor facilitate ovulation by cooperative mechanisms and that they regulate ovarian blood flow in a different manner.

Some Observations on the Sympathetic Nervous System

1939 ◽  
Vol 85 (358) ◽  
pp. 902-902
Author(s):  
E. Arnold Carmichael
Keyword(s):  
Blood Flow ◽  
Nervous System ◽  
Cerebral Blood Flow ◽  
Sympathetic Nervous System ◽  
Arterial Pressure ◽  
Blood Vessels ◽  
Fluid Pressure ◽  
Spinal Fluid ◽  
Cerebral Blood Vessels ◽  
Sympathetic Nervous

Outline of physiology of sympathetic nervous system and its effect on the cerebral blood-vessels. Other factors controlling cerebral blood-vessels, such as local intra-arterial pressure and gas tension. The action of adrenalin-like and cholin-like substances on the cerebral blood-vessels. Alteration in cerebral blood flow during a convulsion, and the accompanying changes in cerebro-spinal fluid pressure. Evidence for systemic sympathetic disturbance during a convulsion. Discussion of “vaso-vagal” attacks and “diencephalitic” epilepsy.

Mg2+–Ca2+ interaction in contractility of vascular smooth muscle: Mg2+ versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels

1987 ◽  
Vol 65 (4) ◽  
pp. 729-745 ◽  
Author(s):  
B. M. Altura ◽  
B. T. Altura ◽  
A. Carella ◽  
A. Gebrewold ◽  
T. Murakawa ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Blood Vessels ◽  
Divalent Cations ◽  
Smooth Muscles ◽  
In Vivo Studies ◽  
Channel Blockers ◽  
Arterial Blood

Contractility of all types of invertebrate and vertebrate muscle is dependent upon the actions and interactions of two divalent cations, viz., calcium (Ca2+) and magnesium (Mg2+) ions. The data presented and reviewed herein contrast the actions of several organic Ca2+ channel blockers with the natural, physiologic (inorganic) Ca2+ antagonist, Mg2+, on microvascular and macrovascular smooth muscles. Both direct in vivo studies on microscopic arteriolar and venular smooth muscles and in vitro studies on different types of blood vessels are presented. It is clear from the studies done so far that of all Ca2+ antagonists examined, only Mg2+ has the capability to inhibit myogenic, basal, and hormonal-induced vascular tone in all types of vascular smooth muscle. Data obtained with verapamil, nimopidine, nitrendipine, and nisoldipine on the microvasculature are suggestive of the probability that a heterogeneity of Ca2+ channels, and of Ca2+ binding sites, exists in different microvascular smooth muscles; although some appear to be voltage operated and others, receptor operated, they are probably heterogeneous in composition from one vascular region to another. Mg2+ appears to act on voltage-, receptor-, and leak-operated membrane channels in vascular smooth muscle. The organic Ca2+ channel blockers do not have this uniform capability; they demonstrate a selectivity when compared with Mg2+. Mg2+ appears to be a special kind of Ca2+ channel antagonist in vascular smooth muscle. At vascular membranes it can (i) block Ca2+ entry and exit, (ii) lower peripheral and cerebral vascular resistance, (iii) relieve cerebral, coronary, and peripheral vasospasm, and (iv) lower arterial blood pressure. At micromolar concentrations (i.e., 10–100 μM), Mg2+ can cause significant vasodilatation of intact arterioles and venules in all regional vasculatures so far examined. Although Mg2+ is three to five orders of magnitude less potent than the organic Ca2+ channel blockers, it possesses unique and potentially useful Ca2+ antagonistic properties.

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