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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Pithed rats were respired at a fixed rate of 54 cycles min-1 and with a ventilation volume of either 20 (control) or 10 ml kg-1. In these two preparations, the dose-response relationships for the systemic blood pressure responses to endothelin-1, administered i.v., were examined. Also, cardiac output, its distribution, tissue blood flows and vascular resistances were determined at both respiratory volumes in pithed rats given saline or during pressor responses to endothelin-1 (750 ng, i.v.). Finally, a comparison was made of the pressor responses to endothelin-1 in the blood perfused superior mesenteric arterial bed of pithed rats respired at 10 or 20 ml kg-1. 2. In control rats the systemic blood pressure responses to i.v. endothelin-1 were biphasic with an initial, transient (30 s) decrease in blood pressure followed by a well sustained pressor response. These responses were dose-dependent (the ED50 for the pressor response being 0.27 +/- 0.04 micrograms). The pressor effect of endothelin-1 was due to an increase in total peripheral resistance with no change in heart rate or cardiac output. This increased total peripheral resistance was due to vasoconstriction of the spleen, stomach, large intestine, small intestine and the pancreas/mesentery (in which it was most severe). Endothelin-1 also increased blood flow through the heart, lungs, liver, epididimides, fat and skin through redistribution of cardiac output to these vascular beds. 3. At the lower ventilation volume there was moderate acidosis, hypoxia and hypercapnia relative to those rats respired at 20 ml kg-1. With respiration at 10 ml kg-1, the pressor response to endothelin-1 was not sustained and, after oscillations in both blood pressure and heart rate, death occurred 15-20 min after administration. The pressor effect resulted from increases in cardiac output (due to increased stroke volume) and total peripheral resistance: the latter was caused by vasoconstriction in the stomach, small intestine, large intestine and pancreas/mesentery. Endothelin-1 increased blood flow through the heart, lungs, liver, kidneys, testes, fat and skin due to either an increase in cardiac output, redistribution of cardiac output or both. 4. Endothelin-1 induced dose-dependent pressor responses in the mesenteric bed in situ. At the lower ventilation volume the potency of endothelin-1 in this vascular bed was increased approximately two fold with the ED50 being 68 +/- 7 pmol compared to 113 +/- 15 pmol in the rats respired at 20 ml kg-1. 5. This study indicates that, in normoxic control pithed rats, the pressor response to endothelin-1 was due largely to vasoconstriction of the splanchnic vascular bed. In rats with moderate hypoxia, hypercapnia and acidosis, the pressor response was due to vasoconstriction of the gastrointestinal tract as well as an increase in cardiac output. Endothelin-1 induced profound vasoconstriction in the mesenteric bed of the pithed rat both in vivo and in situ. The potency of endothelin-1 on this bed in situ was doubled by lowering the ventilation volume. An increase in cardiac contractility and severe gastrointestinal vasoconstriction may be the initial events leading to the eventual toxic effect of endothelin-1 in the hypoxic pithed rat.
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PMID:Effects of moderate hypoxia, hypercapnia and acidosis on haemodynamic changes induced by endothelin-1 in the pithed rat. 251 90

The mechanism of hypertension induced by recombinant human erythropoietin (rHuEPO) is unclear but may include an increase in peripheral vascular resistance. We studied changes of arterial pressure and plasma endothelin in nine consecutive hemodialysis patients before, and 6 and 12 weeks after, starting rHuEPO. In six patients, changes in cardiac index (CI), stroke index (SI) and total peripheral resistance index (TPRI) were measured by bioimpedance, and forearm vascular responsiveness to intra-arterial norepinephrine (30 to 240 pmol/min) and endothelin-1 (5 pmol/min) were assessed. Six healthy age and sex matched subjects also underwent assessment of forearm vascular responsiveness to norepinephrine and endothelin-1. Treatment with rHuEPO significantly increased hemoglobin and mean arterial pressure (MAP). TPRI also increased by 35 +/- 11%. Plasma endothelin, although elevated basally, remained unchanged. Intra-arterial infusion of norepinephrine caused a maximal increase in forearm vascular resistance (FVR) of 17 +/- 9% before rHuEPO, significantly less than the 32 +/- 5% increase in healthy control subjects (P = 0.04). The response increased to 65 +/- 15% (P = 0.03) after 12 weeks rHuEPO treatment (P = 0.51 vs. controls). Endothelin-1 caused a maximal increase of FVR at 60 minutes of 45 +/- 24% before rHuEPO, which was not significantly different from controls, and tended to decrease with rHuEPO therapy. The response to endothelin-1, but not norepinephrine, correlated inversely with MAP (r = -0.52; P = 0.03) and TPRI (r = -0.51; P = 0.04). In conclusion, these studies show that anemia in chronic renal failure is associated with depressed vascular responsiveness to norepinephrine which is restored by rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Erythropoietin enhances vascular responsiveness to norepinephrine in renal failure. 747 68

Endothelin-1 is a potent vasoactive peptide which may play a role in the regulation of vascular resistance through its autocrine/paracrine effects. We have investigated the influence of salt loading on the renal and cardiac production of endothelin-1 in stroke prone spontaneously hypertensive rats, a classical model of hypertension. The results show that the dietary salt intake did not change systolic blood pressure nor the renal expression of the preproendothelin-1 mRNA but increased cardiac expression of the endothelin-1 gene transcript and a concomitant ventricular hypertrophy.
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PMID:Influence of salt loading on the cardiac and renal preproendothelin-1 mRNA expression in stroke-prone spontaneously hypertensive rats. 772 30

Endothelin-1 (ET-1) is a potent cerebrovascular constrictor that has been implicated in brain ischemia. Utilizing the ETA receptor antagonist, BQ-123, the role of ET-1 in ischemic neuronal death following global ischemia was studied. BQ-123, administered ICV, either before and after ischemia or only after ischemia, increased hippocampal CA1 neuron survival in gerbils subjected to transient global ischemia. This study suggests that ETA receptor antagonists might be useful in neuronal salvage following stroke.
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PMID:Peptidic endothelin-1 receptor antagonist, BQ-123, and neuroprotection. 793 21

A report on a cerebro-vascular disease with autosomal dominant inheritance, characterised by stroke-like episodes beginning in early adulthood and progressive dementia, afflicting one family living in Sweden was presented in 1977. Another afflicted member showing gait and coordination disturbances and impaired cognitive functions is now introduced. Magnetic resonance imaging revealed multiple brain lesions indicating ischaemic injuries. Previous autopsy studies of other cases revealed white matter atrophy, multiple infarcts and lacunes. In one patient who had died from a cerebral haemorrhage, obliteration of intracerebral arteries, occasionally with organised thrombi was present. Autopsy material has now been reinvestigated with special attention to changes of intracerebral arterioles. Cases with long duration of the disease presented pronounced fibrous thickening of the wall of numerous intracerebral arterioles, degeneration of smooth muscle cells of the media and obliteration of the lumen. Immunohistochemistry showed marked expression of fibrillary collagen types I, III and V and of the basal lamina components collagen type IV and laminin. These depositions are probably induced by some primary dysfunction of smooth muscle cells or endothelial cells. Perivascular reactive astrocytes with endothelin-1-like immunoreactivity were present in some brain regions. Endothelin-1 is the most powerful vasoconstrictor peptide known to date. Structural remodelling of intracerebral arterial vessels, actions of different vasoactive factors and rheological disturbances may all interfere with local blood flow in this disease and cause the parenchymal changes of the brain.
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PMID:The microvascular changes in cases of hereditary multi-infarct disease of the brain. 800 65

Endothelin-1 (ET-1) is known to have strong vasoactive properties. Contradictory results have been reported with regard to its inotropic effects. This study examined the dose-dependent (500, 1000, 2500, 5000 and 10,000 ng ET-1/kg vs. NaCl controls) hemodynamic and inotropic effects of ET-1 in 53 open-chest rats during and after a 7-min infusion. Besides measurements in the intact circulation the myocardial function was examined by isovolumic registrations independent of peripheral vascular effects. A transient ET-1 induced (500, 1000, 2500, 5000 ng ET-1/kg) decrease of the left ventricular systolic pressure (LVSP) and the mean aortic pressure (AoPmean) was followed by a dose-related rise of these pressures (LVSP: -1%, -1%, +8%, +16% vs. preinfusion values; AoPmean: -11%, +9%, +39%, +52%). Heart rate (HR) was not influenced by ET-1. Due to the dose-dependent decrease of the stroke volume (SV) the cardiac output (CO) was reduced (CO: -8%, -23%, -40%, -50%). After an initial vasodilatation ET-1 elevates the total peripheral resistance (TPR: -1%, +49%, +139%, +215%) dose-dependently. 10,000 ng ET-1/kg was a lethal dose resulting in cardiac failure within minutes (low output). Since the maximum of the isovolumic LVSP (peak LVSP) and the corresponding dP/dtmax (peak dP/dtmax) were unchanged under ET-1, the isovolumic measurements do not indicate a positive inotropic effect of ET-1 in vivo in contrast to published results of in vitro experiments. It may be possible that a direct positive inotropic effect of ET-1 observed in in vitro studies is counterbalanced in vivo by an indirect negative inotropic effect due to the coronary-constrictive effect of ET-1.
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PMID:Hemodynamic and inotropic effects of endothelin-1 in vivo. 801 Sep 34

Endothelin-1, a peptide exhibiting extremely potent cerebral vasoactive properties, is elevated in the cerebrospinal fluid after hemorrhagic stroke and implicated in cerebral vasospasm. The purpose of this study was to determine changes in endothelin in ischemic rat brain by assaying endothelin tissue and extracellular levels. Immunoreactive endothelin levels in ischemic brain tissue following permanent or transient focal ischemia produced by middle cerebral artery occlusion was determined. In addition, endothelin levels were assayed in striatal extracellular fluid collected by microdialysis before, during, and after global ischemia produced by two-vessel occlusion combined with hypotension. Twenty-four hours after the onset of permanent middle cerebral artery occlusion, the ischemic cortex level (0.58 +/- 0.27 fmol/mg protein) of immunoreactive endothelin was significantly (p < 0.05) increased, by 100%, over that in the nonischemic cortex (0.29 +/- 0.13 fmol/mg protein). Transient artery occlusion for 80 min with reperfusion for 24 h also resulted in a similar significant (p < 0.05) increase, 78%, in immunoreactive endothelin in the ischemic zone. Global forebrain ischemia significantly (p < 0.05) increased the level of immunoreactive endothelin collected in striatal microdialysis perfusate, from a basal level of 14.6 +/- 6.7 to 26.5 +/- 7.7 and 26.2 +/- 7.4 amol/microliters (i.e. 82 and 79%). These changes reflect the relative picomolar extracellular concentration increases during ischemia and following reperfusion, respectively. This is the first demonstration of elevated levels of endothelin in focal ischemic tissue and in the extracellular fluid in global ischemia and suggests a role of the peptide in ischemic and postischemic derangements of cerebral vascular function and tissue injury.
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PMID:Endothelin levels increase in rat focal and global ischemia. 811 29

To investigate the effects and elimination of endothelin-1 in humans, an intravenous infusion of endothelin-1 (ET-1) (4 pmol kg-1 min-1 for 20 min) was given to 10 healthy volunteers. Arterial plasma endothelin-1 like immunoreactivity (ET-1-LI) increased eleven-fold. The fractional extraction of ET-1-LI was 41% and 30% across the pulmonary and skeletal muscle vascular beds, respectively. The lung eliminated almost half of the administered ET-1. No fractional extraction was found in the cerebral circulation. The pulmonary oxygen uptake (VO2) was increased slightly by endothelin-1. Across both the cerebral and skeletal muscle vascular beds the arterio-venous oxygen difference decreased (P < 0.05), suggesting vasodilation, the effect lasting up to 1 h after the end of endothelin-1 infusion in the cerebral circulation. Arterial-pulmonary artery oxygen difference increased by 20%. ET-1 infusion led to a decrease in heart rate (10%), cardiac output (14%) and stroke volume (8%) (all with P < 0.05) as well as a 7% increase in mean arterial blood pressure. Pulmonary and systemic vascular resistance increased by 67% and 25%, respectively (P < 0.05). These results demonstrate the regional differences in the removal of circulating endothelin-1, the lung being mainly responsible for the plasma elimination. Endothelin-1 seems to exert both vasoconstrictive and vasodilatory actions in humans, probably depending on differences in receptor populations and endothelium configuration in various vascular beds.
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PMID:Differences in vascular effects and removal of endothelin-1 in human lung, brain, and skeletal muscle. 811 59

In acute cerebral ischemia there are severe damages of endothelium which have been recognized as the stimuli to secrete endothelin-1, an endothelium-derived peptide and the most potent vasoconstrictor ever known. This study was to measure plasma endothelin-1 level in patients with cerebral infarction and explore the relationship between endothelin-1 and ischemic stroke. The possible involvement of endothelin-1 in local regulation of cerebral arterioles was also investigated. Plasma levels of endothelin-1 were measured by radioimmunoassay in 21 patients. Using a micro-video system, the endothelin-1 actions were also observed on rat pial arterioles in vivo, and with incomplete cerebral ischemia model (rat), effect of ischemia affects the endothelin-1 action. There was a marked increase in plasma endothelin-1 level in the patients and the elevation persisted during the acute and subacute period of stroke. There was a positive correlation between the peptide concentration and infarct size (r = 0.655, P < 0.01). In rats, endothelin-1 (dose range: 10(-10) mole/L-10(-7) mole/L) induced a dose-dependent arteriole contraction after subdural administration. Arteriole calibers were decreased by 27.7% +/- 3.8% (10(-9) mole/L), 46.8% +/- 4.9% (10(-8) mole/L) and 78.5% +/- 4.7% (10(-7) mole/L), respectively. Cerebral ischemia significantly enhanced the action of endothelin-1 (96.4% +/- 7.2% vs 58.2% +/- 6.8%). Endothelin-1 plays an important role in regulating local circulation of ischemic brain. The notable and lasting increase in plasma level of endothelin-1 are associated with cerebral ischemia and infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased plasma endothelin-1 concentration in patients with acute cerebral infarction and actions of endothelin-1 on pial arterioles of rat. 814 9

Endothelin-1 (ETL-1), a peptide recently isolated from vascular endothelial cells, acts in cerebral arteries in vitro as a potent and long-lasting vasoconstrictor and has been implicated in the development of cerebral vasospasm. To ascertain whether this new vasoconstrictor has any effect on regulation of the cerebral circulation, we measured plasma ETL-1 concentrations in patients undergoing carotid revascularization and attempted to correlate the variations of venous and arterial plasma ETL-1 with the characteristics of the procedure, including cerebral vasospasm. We prospectively studied 11 patients undergoing a total of 14 carotid surgical revascularization procedures (12 endarterectomies, 2 polytetrafluoroethylene bypass grafts from the common to the internal carotid arteries). Before carotid cross-clamping, blood samples were drawn from the internal jugular vein and the healthy common carotid artery proximal to the occlusive lesion to be treated. After endarterectomy, blood samples were withdrawn from the internal, external, and common carotid arteries. After the release of the last clamp, a final aliquot of blood was withdrawn from the internal jugular vein. After plasma extraction on a C2-ethyl microcolumn, plasma endothelin-like immunoreactivity was measured by means of radioimmunoassay with a polyclonal antibody. In 9 of the 11 patients, internal jugular vein ETL-1 concentration decreased statistically significantly after carotid artery cross-clamping (4.2 +/- 1.4 pg/ml vs. 3.9 +/- 1.1 pg/ml; p < 0.05). In the 2 patients in whom ETL-1 levels failed to drop, a shunt was used during the procedure in 1, and the other was the only patient who had an ipsilateral ischemic postoperative stroke. The decrease in internal jugular vein ETL-1 concentration failed to correlate with any of the cross-clamping times. The level of arterial blood ETL-1 remained steady in the common carotid artery before and after cross-clamping (4.5 +/- 1.5 pg/ml vs. 4.6 +/- 0.9 pg/ml). A small, nonsignificant decrease in ETL-1 level was noted in the external and internal carotid arteries after cross-clamping. The decrease in internal jugular vein ETL-1 levels may in part reflect a compensatory response to carotid artery cross-clamping, which could limit the reduction of local cerebral blood flow.
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PMID:Decrease in internal jugular endothelin levels after carotid cross-clamping during human carotid revascularization procedures. 879 92


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