(Stroke. 1997;28:176-180.)
© 1997 American Heart Association, Inc.
Articles |
Reperfusion Decreases Myogenic Reactivity and Alters Middle Cerebral Artery Function After Focal Cerebral Ischemia in Rats
the Departments of Surgery, Division of Vascular Surgery (M.J.C., J.M.P.), and Pharmacology (N.L.), Oregon Health Sciences University, and Department of Medicine, Portland Veterans Administration Medical Center (A.L.M.), Portland, Ore.
Correspondence to Marilyn J. Cipolla, Department of Surgery, Division of Vascular Surgery, OHSU, 3181 SW Sam Jackson Park Rd, Portland, OR 97201. E-mail cipollam@ohsu.edu.
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Background and Purpose After focal cerebral ischemia, the function of cerebral arteries is critical to maintain cerebrovascular resistance and minimize damage to ischemic brain regions during reperfusion. In this study we examined the contractile function of isolated and pressurized middle cerebral arteries (MCAs) after 2 hours of occlusion with either 1 to 2 minutes or 24 hours of reperfusion using the intraluminal suture model of transient focal ischemia in rats.
Methods MCAs were dissected after 2 hours of occlusion with either 1 to 2 minutes (OCC, n=8) or 24 hours (RPF, n=5) of reperfusion and compared with those of controls that did not have surgery (n=5). Isolated MCAs were mounted on two glass cannulas in an arteriograph chamber that allowed control over transmural pressure (TMP) and measurement of lumen diameter. Responses to changes in TMP (including myogenic reactivity, basal tone, and passive distensibility) and sensitivity to serotonin and acetylcholine were compared.
Results Increasing TMP from 25 to 75 mm Hg caused vasoconstriction and development of tone that was similar in control and OCC arteries: percent tone was 33±5% versus 25±7% (P>.05). In contrast, tone was severely diminished in RPF MCAs after 24 hours of reperfusion: percent tone=8±4% (P<.01). Sensitivity to serotonin was reduced in OCC arteries, increasing the EC50 value from 0.04±0.1 to 0.11±0.02 µmol/L (P<.05); after 24 hours of reperfusion, sensitivity of RPF MCAs was similar to control. Vasodilation to 10.0 µmol/L acetylcholine was significantly impaired only in RPF arteries: percent increased lumen diameter was 19±3% (control) and 13±4% (OCC, P>.05) versus 9±2% (RPF, P<.01). Passively, OCC MCAs were more distensible, which was reversed after 24 hours of reperfusion; RPF vessels had distensibility similar to that of control arteries but thicker arterial walls.
Conclusions Abnormal structure and function of MCAs occur after 2 hours of ischemia, with diminished myogenic reactivity and tone associated with longer reperfusion.
Key Words: cerebral ischemia, focal • middle cerebral artery • myogenic regulatory factors • reperfusion • rats
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Introduction |
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Reperfusion after cerebral ischemia may contribute to cerebral edema and exacerbate ischemic insult to affected regions of the brain.1 2 Normal cerebrovascular function during reperfusion is critical if resistance is to be maintained and tissue damage minimized; however, little is known about postischemic structure and function of cerebral arteries.
Numerous influences, including myogenic, neurogenic, endothelial, and metabolic influences, contribute to normal maintenance of cerebrovascular resistance.3 For example, changes in luminal diameter in response to fluctuations in perfusion pressure, termed myogenic reactivity, are an important component of CBF autoregulation.4 5 Maintenance of basal tone provides a mechanism for alterations in blood flow on demand. Superimposed on this resting tone are the effects of endothelial vasoactive substances as well as reactivity to hormones and neurotransmitters, both of which greatly influence the level of myogenic tone.3 4 Structural features of the vascular wall may also contribute to vascular resistance by influencing distensibility and permeability. In a complex manner, all these factors interact to regulate arterial diameter (tone). This interaction may be abnormal after ischemia and reperfusion.
In the present study we examined cerebral artery structure and function in rats after focal ischemia and reperfusion. MCAs were studied with the use of an experimental system that allowed assessment of arterial responses to changes in intraluminal pressures. Reactivity to vasoconstrictors and vasodilators as well as passive mechanical properties of the arterial wall were evaluated in MCAs after 2 hours of ischemia with 1 to 2 minutes or 24 hours of reperfusion. To our knowledge, this is the first study to examine differences in intrinsic myogenic properties of MCAs after ischemia and reperfusion.
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Materials and Methods |
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Rat MCA Occlusion Model
Male Sprague-Dawley rats (B&K Universal, Fremont, Calif) weighing 270 to 320 g were used for all experiments. Focal cerebral ischemia was accomplished according to the intraluminal suture method of Zea Longa et al.6 Briefly, the rats were anesthetized with a cocktail (1 mL/kg body wt IP) containing 5 mL ketamine (100 mg/mL), 2.5 mL xylazine (20 mg/mL), 1 mL acepromazine (10 mg/mL), and 0.5 mL saline. The right common carotid artery was exposed, and the external carotid artery and its branches were isolated and coagulated. A 4-0 nylon suture with a blunted tip was inserted into the internal carotid artery through the external carotid artery stump and advanced to the anterior cerebral artery, thus occluding the MCA. Body temperature was monitored with a rectal probe and maintained at 37±0.5°C with a heating pad. After 2 hours of MCA occlusion, the animals were reanesthetized with 1.5% to 2.5% halothane in 1 L/min O2 and the suture carefully removed to restore blood flow. Rats were either decapitated within 1 to 2 minutes after withdrawal or after 24 hours of reperfusion. Control rats had no surgery. All procedures were approved by the Institutional Animal Care Committee at Oregon Health Sciences University. Once the rat was decapitated, the brain was removed and immediately placed in cold (4°C), oxygenated PSS.
Preparation of Arterial Segments
Arteries were compared from three types of animals: control rats (n=5) that had no surgery, rats in which the MCA was occluded for 2 hours and reperfused for 1 to 2 minutes (OCC, n=8), and rats in which the MCA was occluded for 2 hours and reperfused for 24 hours (RPF, n=5). The MCA from the occluded side of the brain was carefully dissected, cleared of extraneous connective tissue, and placed in the arteriograph chamber. Dissected arteries (ID=188±8 µm at TMP=75 mm Hg) were mounted on two glass microcannulas suspended above an optical window within the chamber, perfused with PSS, and secured with two strands of nylon thread (diameter=10 µm) on both the proximal and distal cannulas. For these experiments, the distal cannula was closed off so that there was no flow through the vessels.
Pressurized Arteriograph System
The arteriograph system (Living Systems Instrumentation) consisted of a 20-mL chamber with inlet and outlet ports for suffusion of PSS and drugs from a 50-mL reservoir. The PSS was continually recirculated and pumped through a heat exchanger to warm the PSS to 37°C before it entered the arteriograph chamber and was aerated with a gas mixture of 5% CO2/10% O2/85% N2 to maintain a constant pH of 7.4.
TMP was measured and controlled by a servo system that consisted of an in-line pressure transducer, miniature peristaltic pump, and controller connected to the proximal cannula. The arteriograph chamber containing the mounted arteries was placed on an inverted microscope with an attached video camera and monitor to allow for viewing and electronic measurement of lumen diameter. Lumen diameter was measured by the video scan line, which detected the optical contrast of the vessel walls on the video monitor and generated a voltage ramp within the video dimension analyzer that was proportionate to diameter.7 The output of the video dimension analyzer and pressure controller was sent to an IBM-compatible computer via a serial data acquisition system (DATAQ) for visualization of dynamic responses of diameter and TMP, similar to a chart recorder.
Experimental Protocols
Mounted and pressurized arteries were equilibrated at a TMP of 25 mm Hg for 1 hour. We assessed myogenic reactivity and basal tone by increasing TMP stepwise in increments of 25 mm Hg from 25 to 100 mm Hg and recording arterial diameter at each TMP once stable (
5 minutes). The TMP was then decreased to 75 mm Hg for the remainder of the experiment.
After pressure steps and determination of myogenic tone and reactivity to changes in TMP, 5-HT (0.01 to 10.0 µmol/L) was cumulatively added to the arteriograph bath and the diameter recorded for each concentration once a stable contraction was reached. The final dose of 5-HT was washed out with PSS, and an intermediate dose was given to contract the vessels 30% to 50% of maximum. ACh was then cumulatively added (1.0 to 100.0 nmol/L) and the diameter recorded at each dose.
Once dose-response curves were obtained, papaverine (0.01 mmol/L) was added to the bath. Papaverine, a potent smooth muscle cell relaxant, was used to obtain fully relaxed diameters and wall thickness measurements at each TMP from 0 to 125 mm Hg. From these relaxed diameters, percent tone and distensibility were calculated.
Drugs and Solutions
The perfusate and superfusate for all experiments consisted of a bicarbonate-based phosphate buffer (Ringer's PSS), the ionic composition of which was as follows (mmol/L): NaCl 119.0, NaHCO3 24.0, KCl 4.7, KH2PO4 1.18, MgSO4·7H2O 1.17, CaCl2 1.6, EDTA 0.026, and glucose 5.5. PSS was made each week and stored without glucose at 4°C. Glucose was added to the PSS before each experiment. All drugs (5-HT, ACh, and papaverine) were purchased from Sigma Chemical Co. 5-HT and ACh were made fresh daily as stock solutions of 10-3 and 10-4 mol/L. Papaverine was made fresh each week as a stock solution of 10-2 mol/L and stored at 4°C.
Data Calculations and Statistical Analysis
Spontaneous arterial tone was calculated as percent decrease in diameter from the fully relaxed diameter in papaverine at each TMP by the equation [1-(
tone/papav)]*100%, where tone is diameter of vessels with tone and papav is diameter in papaverine. The EC50 for 5-HT, or the amount of agonist necessary to contract the arteries 50% of maximum, was calculated for each artery by first plotting the dose-response curves on a logarithmic scale and extrapolating the value from a best-fit line between 20% and 80% contraction. Responses to ACh were assessed by calculating the percent change in diameter at the maximum dose (10-5 mol/L). Distensibility of each artery was calculated as percent increase in diameter from the diameter at 1 mm Hg, since vessels often collapse at 0 mm Hg. Data are presented as mean±SE. Differences between groups were determined by ANOVA and considered significant at P<.05.
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Myogenic Reactivity and Tone
When TMP was increased in control and OCC arteries, the arteries responded with active vasoconstriction and development of pressure-dependent tone. After 24 hours of reperfusion, however, RPF arteries lacked this response and dilated to increased TMP. The myogenic response after a step increase in TMP from 50 to 75 mm Hg is shown in the graph in Fig 1
. Note that the slope of the line is slightly negative for both control and OCC arteries, suggesting a maintenance of diameter (tone) at higher TMP. The slope of the line is positive for RPF arteries, indicating passive behavior and loss of myogenic reactivity. Decreased basal tone after 24 hours of reperfusion is also demonstrated in Fig 1 by the increased diameter of RPF arteries at each TMP. The percent basal tone present at a TMP of 75 mm Hg in each artery type is shown in Fig 2. The amount of tone was similar in control and OCC arteries (percent tone=32.6±5.3% in control and 25.1±6.8% in OCC arteries) (P>.05) but was significantly decreased in RPF arteries (percent tone=7.8±4.0%) (P<.01 versus both control and OCC arteries).
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) and OCC (
) arteries responded to increased TMP with active vasoconstriction (ie, myogenic reactivity); RPF arteries (
) behaved passively and increased diameter with increased TMP. *P<.05, **P<.01.
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Agonist-Induced Responses
Addition of 5-HT caused dose-dependent vasoconstriction in all artery types, with dose-response curves to 5-HT shown in Fig 3. Sensitivity to 5-HT was significantly diminished in OCC compared with control arteries, with the EC50 value increasing from 0.04±0.01 µmol/L in control to 0.11±0.02 µmol/L in OCC arteries (P<.05). In RPF arteries, sensitivity to 5-HT was restored to the level of control arteries with return of the EC50 to 0.04±0.01 µmol/L (P>.05 versus control, P<.05 versus OCC). Addition of ACh after precontraction with 5-HT caused modest dilation in all MCAs. The percent increase in diameter induced by the highest dose of ACh (10-5 mol/L) was 19.0±2.6% in control arteries, 13.0±3.6% in OCC arteries (P>.05), and 9.0±2.0% in RPF arteries (P<.01 versus control). A graph showing the percent increase in diameter at 10-5 mol/L ACh for each artery type is shown in Fig 4.
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Passive Distensibility and Wall Thickness Measurements
We assessed distensibility of the arterial wall by measuring diameter changes as a function of TMP under fully relaxed conditions in papaverine. A graph showing the percent distensibility as a function of TMP for each artery type is shown in Fig 5. At TMPs greater than 25 mm Hg, OCC arteries were significantly more distensible than control MCAs. Distensibility returned to control levels after 24 hours of reperfusion. Wall thickness was measured by the video dimension analyzer and was accurate within ±1.0 µm. A graph of wall thickness for each artery type as a function of TMP is shown in Fig 6. As can be seen in the graph, the arterial wall becomes thinner as TMP increases. This pattern was consistent for each artery type. However, while the wall thickness of control and OCC arteries was similar, RPF arteries had significantly thicker walls at each TMP.
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Discussion |
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It is generally accepted that cerebral arteries maintain a state of partial constriction or tone that facilitates increases or decreases in arterial diameter, providing a mechanism for modulation of local blood flow.3 4 5 Arterial tone is modulated by surrounding smooth muscle that contracts in response to increased TMP and relaxes in response to decreased TMP, thus contributing to autoregulation of CBF.4 Maintenance of intrinsic myogenic reactivity and tone appears critical for establishing appropriate vascular resistance, thereby protecting downstream arterioles and capillaries during changing perfusion pressures.
The present study demonstrates that myogenic reactivity of RPF arteries was significantly impaired and basal tone severely diminished. OCC arteries responded normally to TMP and demonstrated tone similar to that of control arteries. In contrast, after 24 hours of reperfusion, cerebrovascular resistance appeared impaired, a result that could exacerbate the ischemic insult and contribute to cerebral edema. These findings are consistent with other studies that have demonstrated reperfusion-induced increases in CBF8 and MCA dilation.9 The present study, however, provides the first evidence that arterial responses to changes in TMP are distinctly abnormal after 24 hours of reperfusion.
It is impossible to determine whether the abnormalities detected in RPF arteries were due to reperfusion or the initial ischemic insult. In fact, differentiation between ischemic versus reperfusion events may not be clinically relevant since the physiological outcome may be similar and certainly difficult to separate. In any case, the results of this study clearly demonstrate for the first time that MCAs lack intrinsic myogenic behavior after 2 hours of ischemia with 24 hours of reperfusion. The fact that OCC arteries responded myogenically to TMP and had a normal level of basal tone indicates a possible window of opportunity for treatment.
The arteries of the cerebral circulation are under neurogenic control as well, and the level of tone and cerebrovascular resistance can be modulated by vasoactive responses to neurotransmitters.10 Reactivity to the endogenous neurotransmitter 5-HT was diminished only in OCC arteries, indicating that this response is probably more related to ischemia. While this study does not define the cause of ischemia-induced decrease in 5-HT sensitivity, other studies have demonstrated decreased vasoreactivity to 5-HT in bovine MCA under hypoxic conditions.11 In this study, reactivity to 5-HT returned to control levels after 24 hours of reperfusion.
Endothelial-mediated vasodilation to ACh was significantly diminished in RPF arteries. The responses of the OCC group tended to decrease; however, as a result of highly variable responses, there was insufficient power to detect statistical differences. This observation is important because electron micrographs revealed partial endothelial denudation of both types of occluded vessels, which may contribute to the decreased response (photographs not shown). Endothelial denudation of cerebral arteries after 2 hours of occlusion and reperfusion was also reported by Nishigaya et al12 and is consistent with other studies demonstrating diminished endothelial-mediated relaxation of cerebral arteries after ischemia and reperfusion.13 The present findings, however, indicate that impaired ACh vasodilation after 2 hours of ischemia worsens after 24 hours of reperfusion.
Differences in distensibility were noted only in OCC arteries. This finding is in agreement with a study that detected a significant decrease in type IV collagen content in basal laminae of cerebral arteries after 2 hours of ischemia.14 Differences in passive distensibility of the vascular wall indirectly suggest fundamental alterations in extracellular matrix and/or basal laminar components since the major proteins that constitute the extracellular matrix are collagen IV, which provides tensile strength, and elastin, which determines elasticity.15 Diminished collagen type IV content could contribute to altered passive mechanical properties, including increased distensibility, after ischemia and may reflect significant restructuring of the vascular wall in response to ischemia. Another indication of possible vascular wall restructuring is the observation that MCAs had significantly thicker walls after 24 hours of reperfusion. This new finding may be associated with injury and repair mechanisms evoked during the postischemic period and may relate to increased permeability of cerebral vessels after ischemia and reperfusion.16 17
In conclusion, ischemia followed by reperfusion alters cerebrovascular structure and function. To our knowledge, this is the first study to report diminished myogenic mechanisms after ischemia with 24 hours of reperfusion. In this situation, if no compensatory autoregulatory phenomenon occurs, decreased myogenic reactivity and basal tone may predispose one to vascular and cerebral edema.
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Received July 16, 1996; revision received August 21, 1996; accepted September 25, 1996.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction References |
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1. Siesjo BK. Pathophysiology and treatment of focal cerebral ischemia, I: pathophysiology. J Neurosurg.. 1992;77:169-184.[Medline] [Order article via Infotrieve]
2. Siesjo BK. Pathophysiology and treatment of focal cerebral ischemia, II: mechanisms of damage and treatment. J Neurosurg.. 1992;77:337-354.[Medline] [Order article via Infotrieve]
3. Johnson PC. Review of previous studies and current theories of autoregulation. Circ Res. 1964;14-15(suppl I):I-2-I-9.
4.
Osol G, Halpern W. Myogenic properties of cerebral blood vessels from normotensive and hypertensive rats. Am J Physiol.. 1985;249:H914-H921.
5. Mellander S. Functional aspects of myogenic vascular control. J Hypertens. 1989;7(suppl 4):S21-S30.
6.
Zea Longa E, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke.. 1989;20:84-91.
7.
Wiederhielm CA. Continuous recording of arteriolar dimensions with a television microscope. J Appl Physiol.. 1963;18:1041-1042.
8. Kangstrom E, Smith M-L, Siesjo BK. Local cerebral blood flow in the recovery period following complete cerebral ischemia in the rat. J Cereb Blood Flow Metab.. 1983;3:170-182.[Medline] [Order article via Infotrieve]
9.
Tasdemiroglu E, Macfarlane R, Wei EP, Kontos HA, Moskowitz MA. Pial vessel caliber and cerebral blood flow become dissociated during ischemia-reperfusion in cats. Am J Physiol.. 1992;263:H533-H536.
10. Moskowitz MA, Macfarlane R, Tasdemiroglu E, Wei EP, Kontos HA. Neurogenic control of the cerebral circulation during global ischemia. Stroke. 1990;21(suppl III):III-168-III-171.
11.
Vanall PE, Simeone FA. Effects of oxygen and glucose deprivation on vasoactivity in isolated bovine middle cerebral artery. Stroke.. 1986;17:970-975.
12.
Nishigaya K, Yoshida Y, Sasuga M, Nukui H, Ooneda G. Effect of recirculation on exacerbation of ischemic vascular lesions in rat brain. Stroke.. 1991;22:635-642.
13.
Mayhan WG, Amundsen SM, Faraci FM, Heistad DD. Responses of cerebral arteries after ischemia and reperfusion in cats. Am J Physiol.. 1988;255:H879-H884.
14.
Hamann GF, Okada Y, Fitridge R, del Zoppo GJ. Microvascular basal lamina antigens disappear during cerebral ischemia and reperfusion. Stroke.. 1995;26:2120-2126.
15. Abrahamson DR. Recent studies on the structure and pathology of basement membranes. J Pathol.. 1986;149:257-278.[Medline] [Order article via Infotrieve]
16. Pulsinelli W. Pathophysiology of acute ischaemic stroke. Lancet.. 1992;339:533-536.[Medline] [Order article via Infotrieve]
17. Yang G-Y, Betz AL. Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats. Stroke.. 1994;25:1658-1665.[Abstract]
Editorial Comment
School of Medicine, Medical College of Virginia, Richmond, Va
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The recent demonstration that thrombolytic therapy is effective in restoring reperfusion and in relieving ischemia caused by thrombotic occlusion of cerebral arteries increases the urgency for a better understanding of the effects of reperfusion on neuronal and cerebral vascular function.
The accompanying article by Cipolla et al evaluated vascular function in isolated MCAs after experimental regional ischemia either after a very short period of reperfusion or after 24 hours of reperfusion. They found loss of vascular tone, diminished responsiveness to the vasoconstrictor effect of 5-HT, abolition of the endothelium-dependent relaxation from ACh, and diminished distensibility. Some of these findings have been reported previously in other studies of ischemia/reperfusion of the brain in a variety of experimental preparations. The importance of this article is that it extends the studies to 24 hours after reperfusion and that the approaches used by the authors provide the opportunity to study the vessels in vitro in the absence of influences from the parenchyma. These abnormalities may be expected to have serious consequences for cerebral vascular function, which may in turn affect neuronal function.
The article by Cipolla et al does not address the mechanism of these vascular abnormalities. Obviously, if effective therapeutic intervention is to be instituted, the mechanism of the abnormalities must be understood more clearly.
Earlier findings have provided clues to the mechanisms involved. As the authors point out in the article, the diminished distensibility is very likely due to increased deposition of collagen in the vessel wall. Also, it is well established that during reperfusion there is increased oxygen radical generation and that these agents interact with endothelium-derived relaxing factor and inactivate it.1R This is the mechanism for the elimination of the endothelium-dependent relaxation by ACh and other vasodilators that act on the endothelium. However, some of the studies that have addressed this issue have shown that superoxide production occurs early in the period of reperfusion and, at least for short periods of occlusion, is short-lasting. In fact, after a short period of occlusion in the cerebral microcirculation, the abnormalities in the endothelium-dependent relaxation to acetylcholine are transient and return spontaneously to the normal state after a relatively short period of time.1R Little is known about the mechanisms that account for reduction in tone and loss of myogenic activity. The reduced response to 5-HT may reflect abnormalities in the overall contractile mechanism of vascular smooth muscle, changes in receptor density, or reduced production and release of endothelium-derived contracting factor. There is evidence consistent with the last mechanism in experimental brain trauma.2R It is evident that this remains a fertile area for future research.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction References |
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1R. Nelson CW, Wei EP, Povlishock JT, Kontos HA, Moskowitz MA. Oxygen radicals in cerebral ischemia. Am J Physiol.. 1992;263:H1356-H1362.
2R. Kontos HA, Wei EP. Endothelium-dependent responses after experimental brain injury. J Neurotrauma.. 1992;9:349-354.[Medline] [Order article via Infotrieve]
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