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.

Effects of cocaine, benzoylecgonine, and cocaine metabolites in cannulated pressurized fetal sheep cerebral arteries

1994 ◽  
Vol 77 (2) ◽  
pp. 834-839 ◽  
Author(s):  
M. D. Schreiber ◽  
J. A. Madden ◽  
R. F. Covert ◽  
L. J. Torgerson
Keyword(s):  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Receptor Subtypes ◽  
Cocaine Exposure ◽  
Response Curves ◽  
Fetal Sheep ◽  
Prenatal Cocaine Exposure ◽  
Cocaine Metabolites ◽  
Prenatal Cocaine

Prenatal cocaine exposure has been reported to cause neurovascular complications in the developing fetus. To determine the effect of cocaine on the fetal neurovasculature, we studied the in vitro response of fetal sheep cerebral arteries to cocaine and cocaine metabolites. The change in diameter of cannulated pressurized cerebral artery segments from fetal sheep was measured using a video microscaler system. Cumulative dose-response curves (10(-12)-10(-4) M) were generated for cocaine and the major cocaine metabolites in fetal sheep cerebral artery segments. Benzoylecgonine (> 10(-10) M) also caused concentration-dependent constriction, and cerebral artery segments were significantly more sensitive to benzoylecgonine than to cocaine and the other cocaine metabolites. Benzoylecgonine-induced vasoconstriction appeared to be mediated through alpha-adrenergic stimulation, predominantly through stimulation of alpha 1-adrenergic receptor subtypes. We conclude that cocaine and benzoylecgonine cause significant fetal cerebral artery vasoconstriction in vitro. Cocaine and benzoylecgonine-induced cerebral vasoconstriction may contribute to the perinatal neurovascular complications associated with prenatal cocaine exposure.

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.

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.

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.

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.

Cerebral arterial spasm

1974 ◽  
Vol 40 (4) ◽  
pp. 433-441 ◽  
Author(s):  
George S. Allen ◽  
Lavell M. Henderson ◽  
Shelly N. Chou ◽  
Lyle A. French
Keyword(s):  
Small Volume ◽  
Contractile Activity ◽  
Cerebral Arteries ◽  
Arterial Spasm ◽  
Vasoactive Agents ◽  
Response Curves ◽  
Content Type ◽  
Middle Cerebral Arteries ◽  
Fine Print

✓ In vitro experiments were performed using a small volume chamber to determine the contractile activity of various vasoactive agents on the canine basilar and middle cerebral arteries. Cumulative dose-response curves were obtained for most of the agents tested including serotonin and three different prostaglandins; many of these curves were found to be similar for segments from both arteries. It was concluded from these curves, and the known concentrations in blood, that serotonin is probably the agent in blood responsible for the cerebral arterial spasm that often follows a subarachnoid hemorrhage. This in vitro method is capable of detecting serotonin concentrations as low as 10−12 gm/ml and may prove useful as a quantitative and well-controlled method for studying the etiology of spasm and the receptor mechanisms present in the cerebral arteries.

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.

Vascular reactivity in experimental portal hypertension

1987 ◽  
Vol 252 (2) ◽  
pp. G158-G162 ◽  
Author(s):  
A. Bomzon ◽  
L. M. Blendis
Keyword(s):  
Portal Hypertension ◽  
Vascular Reactivity ◽  
Phase 1 ◽  
Portal Pressure ◽  
Slow Phase ◽  
Response Curves ◽  
Portal Vein Stenosis ◽  
Vascular Responsiveness ◽  
Vein Stenosis

Portal hypertension (PHT) is known to be associated with a hyperdynamic circulation, yet the pathogenesis of both remains unclear. Therefore, we have studied serially the relationship between portal pressure and in vitro peripheral vascular responsiveness in an animal model of presinusoidal PHT. In rats with partial portal vein stenosis (PPVS) or sham-operated (SO) controls, we studied contractile responses to cumulative doses of norepinephrine (NE) and to a single dose of 0.8 microM NE of 20-mm helically cut strips of thoracic aorta. At both 2 and 10 days postoperatively, the portal pressures (mean intrasplenic pressure) in PPVS, 14.3 +/- 1.5 mmHg and 14.1 +/- 1.3 mmHg were significantly elevated compared with SO controls, 7.6 +/- 0.6 mmHg (P less than 0.005) and 9.7 +/- 0.5 mmHg (P less than 0.01), respectively. Yet, there was no significant differences between the two groups in the Rmax and ED50 of the contractile response curves to cumulative doses of NE as well as in the fast (phase 1) and slow phase (phase 2) of the contraction to 0.8 microM NE. In contrast, at 21 days, portal pressure in the PPVS rats fell to 11.0 +/- 0.7 mmHg but remained significantly higher than that of the SO controls, 8.2 +/- 1.0 mmHg (P less than 0.05). This occurred in conjunction with a significant decrease in Rmax [698 +/- 87 mg (PPVS) vs. 1148 +/- 92 mg (SO); P less than 0.005] but no significant change in ED50, indicating a decreased sensitivity to NE due to an alteration in alpha-adrenoreceptor function.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Nitric oxide does not mediate the attenuated pulmonary vascular reactivity of chronic pneumonia

1993 ◽  
Vol 265 (3) ◽  
pp. H943-H948 ◽  
Author(s):  
A. Yaghi ◽  
N. A. Paterson ◽  
D. G. McCormack
Keyword(s):  
Nitric Oxide ◽  
Vascular Reactivity ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Induced Voltage ◽  
Response Curves ◽  
Contractile Responses ◽  
Vascular Contractility ◽  
Vascular Responsiveness

Chronic Pseudomonas pneumonia is associated with decreased acute hypoxic pulmonary vasoconstriction. However, it is not known whether this is a result of a generalized reduction in contractile responsiveness. We therefore examined the effect of chronic Pseudomonas pneumonia on in vitro pulmonary vascular responsiveness to agonists. We then investigated the role of nitric oxide (NO) in the altered pulmonary vascular contractility. Control rats or rats infected with Pseudomonas (pneumonia) were killed, and small intrapulmonary arteries (100-200 microns effective lumen radius) were removed. In the pneumonia group, arteries were harvested from the pneumonic area of the lung. Vascular responsiveness was assessed in vitro by obtaining cumulative dose-response curves to contractile agonists [phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha), and KCl]. KCL-induced (voltage-operated) contractions were not significantly depressed in small pulmonary arteries from pneumonic lungs, suggesting that the smooth muscle contractile apparatus in these arteries was preserved. Contractile responses to the three receptor-operated agonists (PE, 5-HT, and PGF2 alpha) were significantly depressed in arteries subserving the pneumonic lobe of infected rats. NG-monomethyl-L-arginine, which blocks the synthesis of NO, caused a shift toward the left in the dose-contraction curves to PE, PGF2 alpha, and 5-HT in vessels from the sterile control lungs, but it had little effect on arteries from the pneumonic lungs. Chronic Pseudomonas pneumonia is associated with depressed pulmonary vascular contractility in vitro, particularly affecting the receptor-mediated contractile responses. Excessive NO release does not contribute to this attenuated vascular contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

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