Comparison of responses to vasoactive drugs in human and rat cerebral arteries using myography and pressurized cerebral artery method

Cephalalgia ◽  
2012 ◽  
Vol 33 (3) ◽  
pp. 152-159 ◽  
Author(s):  
Gustaf Grände ◽  
Elisabeth Nilsson ◽  
Lars Edvinsson
Keyword(s):  
Cerebral Artery ◽  
Species Differences ◽  
Cerebral Arteries ◽  
Noticeable Effect ◽  
Vasoactive Substances ◽  
Dilatory Response ◽  
Luminal Side ◽  
Human Arteries ◽  
Cranial Vessels

Background Dilatation of cranial vessels has been proposed as a part of the cascade that initiates an episode of migraine. This is based on the observation that intravenous administration of several substances with vasodilator properties can trigger migraine-like symptoms in migraineurs. Methods We used in vitro myography of human cerebral arteries and in vitro pressurized arteriography of rat middle cerebral artery (MCA) to evaluate the vasomotor responses of cerebral arteries to increasing concentrations of vasoactive substances used to elicit migraine-like attacks. Results All substances except carbachol induced a strong vasodilatory response when applied to the abluminal side of a rat MCA but negligible response when applied to the luminal side. Luminal carbachol gave a strong dilatory response but a weak response at the abluminal side. The prostaglandins PGE2 and epoprostenol constricted the rat MCA while human cerebral arteries relaxed. The pEC50 of carbachol, histamine, epoprostenol, VIP and sildenafil differed significantly between cerebral arteries from man and rat. The differences in pEC50 for SNP, αCGRP, PACAP-27 and PACAP-38 were not significant between the species. PGE2 had no noticeable effect on human arteries in vitro. Conclusion All tested substances with the exception of VIP and carbachol have been found to elicit migraine-like attacks in migraineurs. Since these two agents have vasodilatory effects in humans, it suggests that vasodilatation is not the only reason for eliciting a migraine-like attack in migraineurs. In addition, there are significant species differences that show the importance of performing experiments in human vessels.

Mechanics of large and small cerebral arteries in chronic hypertension

1994 ◽  
Vol 266 (3) ◽  
pp. H1027-H1033 ◽  
Author(s):  
M. A. Hajdu ◽  
G. L. Baumbach
Keyword(s):  
Cerebral Artery ◽  
Posterior Cerebral Artery ◽  
Cerebral Arteries ◽  
Internal Diameter ◽  
Chronic Hypertension ◽  
External Diameter ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

The goal of this study was to investigate factors that contribute to reductions in internal diameter of large and small cerebral arteries during chronic hypertension. We measured diameter of second- and third-order branches of the posterior cerebral artery in vitro during maximal dilation with EDTA in 6-mo-old stroke-prone spontaneously hypertensive rats (SHRSP, n = 7) and Wistar-Kyoto rats (WKY, n = 7). Cross-sectional area of the vessel wall, measured histologically, was not significantly different at 70 mmHg in SHRSP and WKY in large or small branches of posterior cerebral artery. In large branches of posterior cerebral artery, external and internal diameters were significantly less at 70 mmHg in SHRSP than in WKY, whereas external and internal diameters converged at 0 mmHg in the two groups of rats. In small branches, on the other hand, external and internal diameters were significantly less at all levels of intravascular pressure in SHRSP than in WKY. The stress-strain relation in posterior cerebral artery of SHRSP was shifted to the left in large branches and to the right in small branches, which indicates that distensibility was reduced in large cerebral arteries of SHRSP and increased in small cerebral arteries. These findings suggest that different mechanisms are responsible for impairment of maximal dilator capacity in large and small cerebral arteries of SHRSP: reduced distensibility in large arteries and remodeling with reduced external diameter in small arteries. Furthermore the findings provide additional support for the concept that hypertrophy may not be a primary factor in impaired maximal dilation.

Dose responses of cerebral arteries of the dog, rabbit, and man to human hemoglobin in vitro

1980 ◽  
Vol 53 (4) ◽  
pp. 486-490 ◽  
Author(s):  
Glyn R. Wellum ◽  
Thomas W. Irvine ◽  
Nicholas T. Zervas
Keyword(s):  
Cerebral Arteries ◽  
Postmortem Changes ◽  
Human Hemoglobin ◽  
Content Type ◽  
Weak Response ◽  
Basilar Arteries ◽  
Human Arteries ◽  
Dose Responses ◽  
Fine Print

✓ Dose responses in vitro of the basilar arteries of the dog, rabbit, and man to human hemoglobin are reported. For each species, the response occurred over a range of 10−9M to greater than 10−5M hemoglobin. When compared to a maximum serotonin contraction, the relative constriction induced by 10−5M hemoglobin was greater in the rabbit than in the dog, which in turn was greater than in man. The comparatively weak response of the human arteries is probably attributable to postmortem changes.

Enhanced myogenic tone in cerebral arteries from a rabbit model of subarachnoid hemorrhage

2002 ◽  
Vol 283 (6) ◽  
pp. H2217-H2225 ◽  
Author(s):  
Masanori Ishiguro ◽  
Corey B. Puryear ◽  
Erica Bisson ◽  
Christine M. Saundry ◽  
David J. Nathan ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Rabbit Model ◽  
Small Diameter ◽  
Myogenic Tone ◽  
The Impact ◽  
Intravascular Pressure

Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Currently, little is known regarding the impact of SAH on small diameter (100–200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. With the use of a rabbit SAH model and in vitro video microscopy, cerebral artery diameter was measured in response to elevations in intravascular pressure. Cerebral arteries from SAH animals constricted more (∼twofold) to pressure within the physiological range of 60–100 mmHg compared with control or sham-operated animals. Pressure-induced constriction (myogenic tone) was also enhanced in arteries from control animals organ cultured in the presence of oxyhemoglobin, an effect independent of the vascular endothelium or nitric oxide synthesis. Finally, arteries from both control and SAH animals dilated as intravascular pressure was elevated above 140 mmHg. This study provides evidence for a role of oxyhemoglobin in impaired autoregulation (i.e., enhanced myogenic tone) in small diameter cerebral arteries during SAH. Furthermore, therapeutic strategies that improve clinical outcome in SAH patients (e.g., supraphysiological intravascular pressure) are effective in dilating small diameter cerebral arteries isolated from SAH animals.

scholarly journals Endotoxin Decreases the Contractile Responses of the Porcine Basilar Artery to Vasoactive Substances

1993 ◽  
Vol 13 (4) ◽  
pp. 712-719 ◽  
Author(s):  
Masami Ueno ◽  
Tony J.-F. Lee
Keyword(s):  
Endothelial Cells ◽  
Basilar Artery ◽  
Muscle Tone ◽  
Cerebral Arteries ◽  
Contractile Responses ◽  
Vasoactive Substances ◽  
Basilar Arteries ◽  
Arterial Reactivity ◽  
Lps Treatment

The effects of endotoxin (lipopolysaccharide; LPS) on the reactivity of isolated porcine basilar artery were examined using in vitro tissue bath techniques. The active muscle tone of the basilar arterial rings with or without endothelial cells induced by U46619 (1 μ M) reached a plateau in 15 min, which was stable for the first hour and gradually decreased during the next 5 h. This time-dependent decrease in tone was significantly potentiated in the presence of LPS (20 μg/ml). The potentiation by LPS was blocked by Nw-nitro-l-arginine (l-NNA; 60 μ M), methylene blue (10 μ M), and dexamethasone (1 μ M) but not by hemoglobin (1 μ M). The effect of l-NNA was readily reversed by l-arginine but not by d-arginine. Furthermore, the contractile responses of porcine basilar arterial rings with or without intact endothelium to U46619 and KCl were decreased following incubation with LPS (20 μg/ml) for 4 h. Similar hyporeactivity was observed in cold storage–denervated cerebral arteries incubated with LPS for 4 h. This decrease in contractile responses in LPS-treated rings was reversed by 60 μ M l-NNA and 1 μ M dexamethasone. These results indicate that LPS treatment renders the porcine basilar arteries hyporesponsive to vasoconstrictors. Since effects of LPS were not modified by the presence of endothelial cells and perivascular neurons, the alteration in cerebral arterial reactivity may be due in part to an enhanced formation of nitric oxide from l-arginine in the vascular smooth muscle cells.

scholarly journals Norepinephrine and Acetylcholine Transmitter Mechanisms in Large Cerebral Arteries of the Pig

1982 ◽  
Vol 2 (4) ◽  
pp. 439-450 ◽  
Author(s):  
Tony Jer-Fu Lee ◽  
L. R. Kinkead ◽  
S. Sarwinski
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cerebral Artery ◽  
Direct Action ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Direct Stimulation ◽  
Low Concentration

This study examines, using an in vitro tissue bath technique, the nature of the transmitter mechanism(s) in the pig cerebral artery. Of the arteries with intact endothelium, about 25% relaxed on application of acetylcholine (ACh) at low concentration (3 × 10−7 to 3 × 10−6 M) and constricted at concentrations exceeding 10−5 M. The remaining arterial preparations either constricted (61%) or exhibited no response (14%) at any concentration of ACh tested (3 × 10−7 to 3 × 10−3 M). On the other hand, none of the arteries without endothelium relaxed at any concentration of ACh tested (3 × 10−7 to 3 × 10−3 M); of these, 90% constricted and 10% exhibited no response. These results show that ACh-induced cerebral vasodilation is dependent on endothelial cells and the direct action of ACh on the vascular smooth muscle cells is constriction. Contrary to findings in the large cerebral arteries of the cat and several other species, about 90% of the pig cerebral arteries, with or without endothelium, dilated upon application of norepinephrine (NE) at low concentration (10−7 to 3 × 10−5 M) and constricted at concentrations exceeding 3 × 10−5 M. The NE dose–response relationships were not different in arteries with and without endothelial cells, indicating that the NE-induced vasodilation was independent of the endothelial cells. The relaxation and constriction were blocked by the respective β- and α-receptor antagonists, suggesting that both responses resulted from direct stimulation by NE of β and α receptors on the smooth muscle cells. Transmural nerve stimulation (TNS) consistently induced vasodilation of the arteries whether or not the endothelial cells were present. The vasodilation was abolished by tetrodotoxin (TTX) and cold storage denervation. The TNS-induced vasodilation was not smaller in arteries without endothelium than in those with endothelium. This suggests that TNS-induced vasodilation was independent of the endothelial cells. When examined histochemically, the pig cerebral artery exhibited rich catecholamine fluorescence. Biochemical assays indicate that NE is the primary catecholamine. However, the TNS-induced vasodilation was not affected by atropine, guanethidine, or propranolol, nor prevented by reserpine. It is suggested that an as yet unidentified transmitter is responsible for the TNS-induced vasodilation. Results of this study suggest that the nerve-released ACh is a potential vasoconstrictor transmitter and that NE is a potential vasodilator transmitter in the large cerebral artery of the pig. The neurogenic control of the pig cerebral circulation may be different from that of other species, including humans.

Concentration-dependent effects of cocaine on monoamine-induced constriction of cannulated, pressurized cerebral arteries from fetal sheep

1995 ◽  
Vol 7 (5) ◽  
pp. 1389
Author(s):  
MD Schreiber ◽  
JA Madden ◽  
RF Covert ◽  
MB Hershenson ◽  
LJ Torgerson
Keyword(s):  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Na Channel ◽  
Monoamine Neurotransmitter ◽  
Response Curves ◽  
Fetal Sheep ◽  
Uptake Inhibition ◽  
Channel Inhibition ◽  
Vascular Responsiveness

Drugs, such as cocaine, which may alter monoamine neurotransmitter responsiveness, could adversely affect the regulation of cerebral vasculature. Cocaine exhibits at least two mechanisms that may alter vascular responsiveness: synaptic uptake inhibition, which may augment response to stimulation, and Na+ channel inhibition, which may attenuate response. To help elicit the concentration-dependent effects of cocaine, the effects of cocaine on monoamine neurotransmitter responsiveness were studied in vitro on fetal sheep cerebral arteries (120 days gestation). The changes in diameter of segments of cannulated, pressurized fetal sheep cerebral artery were measured with a videomicroscaler system. Cumulative concentration-response curves (10(-10) to 10(-4)M) were generated for two monoamines, norepinephrine and serotonin, alone and in the presence of cocaine (10(-5) or 10(-4)M). Cocaine caused concentration-dependent alteration of response. At 10(-4)M, cocaine attenuated mean maximal norepinephrine-induced vasoconstriction 46.2% (P < 0.05). At 10(-5)M, cocaine increased sensitivity to norepinephrine (log EC50 decreased -6.63 +/- 0.09 to -7.11 +/- 0.03) and to serotonin (log EC50 decreased -7.24 +/- 0.04 to -7.81 +/- 0.09) (P < 0.05). The higher concentration of cocaine (10(-4)M) did not significantly decrease log EC50 norepinephrine. Cocaine (10(-4)M) also attenuated the response to single doses of norepinephrine (10(-6)M) and serotonin (10(-6)M) by 26.5% and 40.0%, respectively (P < or = 0.05). It is concluded that cocaine has concentration-dependent effects on vasoconstriction of the fetal sheep cerebral artery in vitro. This cocaine-induced alteration of cerebral vascular responsiveness to monoamines may be important in the regulation of fetal cerebral blood flow.

An In Vitro Patient-Specific Biological Model of the Cerebral Artery Reproduced with a Membranous Configuration for Simulating Endovascular Intervention

2005 ◽  
Vol 17 (3) ◽  
pp. 327-334 ◽  
Author(s):  
Seiichi Ikeda ◽  
◽  
Fumihito Arai ◽  
Toshio Fukuda ◽  
Makoto Negoro ◽  
...  
Keyword(s):  
Cerebral Artery ◽  
Surgical Simulation ◽  
Medical Training ◽  
System Development ◽  
Cerebral Arteries ◽  
Cerebrovascular Diseases ◽  
Endovascular Intervention ◽  
Patient Specific ◽  
Surgical Robots

We propose an in vitro patient-specific anatomical model of the human cerebral artery and its simulation of endovascular intervention, a potent treatment modality for cerebrovascular diseases. Our proposed model reproduces the 3-dimensional vasculature lumen, using computed tomography (CT) and magnetic resonance (MR) fluoroscopic information, within a thin artery-like membranous configuration having material properties close to arterial tissue. This cerebral arterial model reproduces an exceedingly realistic surgical feel, dynamic vascular deformation and, other important aspects involving endovascular intervention, realizing a highly realistic surgical simulation. We also propose another vasculature model that reproduces the subarachnoid space around the cerebral arteries. This version simulates endovascular intervention realistically. The model is compatible with current major imaging modalities such as CT, MR, and transcranial Doppler (TDC), and should provide effective platforms for applications, such as diagnosis, surgical planning, medical training, hemodynamic analysis and medical system development and evaluation, especially surgical robots.

scholarly journals Mechanisms of Action of Endothelin on Isolated Feline Cerebral Arteries: In vitro Pharmacology and Electrophysiology

1989 ◽  
Vol 9 (6) ◽  
pp. 743-747 ◽  
Author(s):  
I. Jansen ◽  
B. Fallgren ◽  
L. Edvinsson
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Contractile Response ◽  
Cerebral Arteries ◽  
Extracellular Calcium ◽  
Maximum Response ◽  
Strong Concentration ◽  
Mechanical Removal ◽  
In Vitro Pharmacology

Vascular endothelium has been found to produce a strong and potent vasoconstrictor peptide, endothelin. In this study, we have examined basic mechanisms underlying the contractile response of cerebral vessels to endothelin using in vitro pharmacology and electrophysiology. It was found that endothelin produced strong concentration-dependent contractions of circular segments of the feline middle cerebral artery. The response was slow in onset and long lasting. The vessels showed a remarkably strong tachyphylactic reaction upon repeated exposure to endothelin. The contractile effect of endothelin was not modified by the α-adrenoceptor antagonist phen-tolamine (10−6 M) or the 5-hydroxytryptamine antagonist ketanserin (10−6 M). Mechanical removal of the endothelium decreased potassium contractions while the maximum response to endothelin was only slightly reduced. There was no change in sensitivity of the cerebral artery to endothelin. The addition of a calcium antagonist (10−6 M diltiazem or 3 × 10−8 M nimodipine) or removal of extracellular calcium from the buffer solution did not change the sensitivity of the artery to endothelin but the maximum response to endothelin was reduced by between 40 and 60% by these procedures. The resting membrane potential of the cat middle cerebral artery was –62.8 ± 3.5 mV. There was no significant depolarization in conjunction with cumulative administration of endothelin in concentrations below 1 × 10−9 M. However, bursts of excitatory junction potentials were occasionally seen in response to high concentrations of endothelin (5 × 10−9 M). The findings suggest that the contractile response to endothelin of cat cerebral arteries involved influx of extracellular calcium through voltage-sensitive calcium channels and is in part mediated via a voltage-insensitive mechanism. Further work is necessary to define the intracellular actions of endothelin.

scholarly journals Estrogen reduces mouse cerebral artery tone through endothelial NOS- and cyclooxygenase-dependent mechanisms

2000 ◽  
Vol 279 (2) ◽  
pp. H511-H519 ◽  
Author(s):  
Greg G. Geary ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Estrogen Replacement ◽  
Luminal Diameter ◽  
Small Resistance ◽  
Oxide Synthase

Gender and estrogen status are known to influence the incidence and severity of cerebrovascular disease. The vasoprotective effects of estrogen are thought to include both nitric oxide-dependent and independent mechanisms. Therefore, using small, resistance-sized arteries pressurized in vitro, the present study determined the effect of gender and estrogen status on myogenic reactivity of mouse cerebral arteries. Luminal diameter was measured in middle cerebral artery segments from males and from females that were either untreated, ovariectomized (OVX), or OVX with estrogen replacement (OVX + EST). The maximal passive diameters of arteries from all four groups were similar. In response to increases in transmural pressure, diameters of arteries from males and OVX females were smaller compared with diameters of arteries from either untreated or OVX + EST females. In the presence of N G-nitro-l-arginine methyl ester, artery diameters decreased in all groups, but diameters remained significantly smaller in arteries from males and OVX females compared with untreated and OVX + EST females. After endothelium removal or when inhibition of nitric oxide synthase and cyclooxygenase were combined, differences in diameters of arteries from OVX and OVX + EST were abolished. These data suggest that chronic estrogen treatment modulates myogenic reactivity of mouse cerebral arteries through both endothelium-derived cyclooxygenase- and nitric oxide synthase-dependent mechanisms.

scholarly journals Responses of Isolated Feline and Human Cerebral Arteries to Prostacyclin and Some of its Metabolites

1983 ◽  
Vol 3 (2) ◽  
pp. 238-245 ◽  
Author(s):  
Tore Uski ◽  
Karl-Erik Andersson ◽  
Lennart Brandt ◽  
Lars Edvinsson ◽  
Bengt Ljunggren
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Basilar Artery ◽  
Species Differences ◽  
Cerebral Arteries ◽  
Pial Arteries ◽  
Contractile Effect ◽  
Resting Tension ◽  
As Species ◽  
Middle Cerebral Arteries

The effects of prostacyclin (PGI2) were studied in isolated cat basilar and middle cerebral arteries and in human pial arteries. In feline vessels with low resting tension, PGI2 had a contractile effect that reached a maximum of 132% (basilar artery) and 23% (middle cerebral artery) of the potassium-induced (127 m M) contraction. In potassium-contracted feline vessels, PGI2 caused a further contraction. When these vessels were contracted by PGF2α, PGI2 induced relaxation, which was most marked in the middle cerebral artery. PGI2 consistently relaxed the middle cerebral artery contracted by the prostaglandin endoperoxide analogue U-44069, whereas the basilar artery was almost unaffected. In human pial arteries with low resting tension, PGI2 had no effects in concentrations below 10−6 M, whereas higher concentrations induced contractions. In potassium-contracted (35 or 127 m M) preparations, PGI2 in concentrations below 10−6 M produced relaxation; in higher concentrations further contraction was induced. Human pial arteries contracted by PGF2α, U-44069, noradrenaline, or 5-hydroxytryptamine consistently relaxed in response to PGI2 (< 10−6 M). The PGI2 metabolite 6-keto-PGE1 had effects similar to those of PGI2, but proved to be less potent on human pial vessels. 6-Keto-PGF1α was ineffective, whereas 6, 15-diketo-PGF1α had minor relaxant effects. The results suggest that consideration must be given to regional as well as species differences concerning the cerebrovascular effects of PGI2.

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