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

Endothelial dysfunction appears to be an early event in most forms of cardiovascular disease. The dysfunction may involve a decreased formation, inactivation, or action of nitric oxide or prostacyclin as well as an increased formation of contracting factors, eg, prostaglandin H2 and endothelin-1. Cardiovascular drugs can improve endothelial function either indirectly through their effects on cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes or directly through endothelial actions. Direct and indirect endothelial protective effects of cardiovascular drugs may significantly contribute to normal organ perfusion and a reduced incidence of myocardial infarction, stroke, and renal failure in patients. Endothelium-dependent vascular regulation in health and in various cardiovascular diseases as well as the effects of currently available cardiovascular drugs are reviewed.
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PMID:Possibilities and perspectives of pharmacotherapy for endothelial protection. 792 59

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

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

This study was designed to assess whether blocking endogenous endothelin with anti-endothelin antibodies could alter the development of hypertension in stroke-prone spontaneously hypertensive rats (SHR) and DOCA-salt treated rats. Specific anti-endothelin antibodies were produced in rabbits by standard methods. The amount of anti-endothelin antibodies employed in this study blocked the hypertensive effect of endothelin-1, 750 ng/kg, by 55% in conscious rats. Intravenous injection of anti-endothelin antibodies as a bolus twice a week for 3 weeks did not affect the rise in blood pressure of stroke-prone SHR (268 +/- 8 mmHg, n = 8) compared to control stroke-prone SHR (256 +/- 7 mmHg, n = 8) treated with normal rabbit serum. Intravenous administration of anti-endothelin antibodies in a same manner also failed to alter the development of hypertension in DOCA-salt treated rats (160 +/- 6 mmHg in anti-endothelin antibodies-treated group, n = 7 compared to 164 +/- 5 mmHg in normal rabbit serum-treated group, n = 7). The administration of anti-endothelin antibodies did not induce any significant changes in body weight, urine volume and urinary sodium excretion in stroke-prone SHR and DOCA-salt treated rats compared to those treated with normal rabbit serum. These findings suggest that circulating endothelin might not play a major role in the regulation of blood pressure in stroke-prone SHR and DOCA-salt treated rats.
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PMID:Chronic treatment with anti-endothelin antibodies fails to modify the development of hypertension in stroke-prone spontaneously hypertensive rats and DOCA-salt hypertensive rats. 821 68

1. The effect of transient forebrain ischemia on endothelin-1 (ET-1) and endothelin-3 (ET-3) production in the hippocampus of stroke-prone spontaneously hypertensive rats (SHRSPs) was investigated using immunohistochemical techniques. 2. In SHRSPs subjected to 10-min bilateral carotid occlusion, neuronal degeneration in the CA1 pyramidal cell layer of the hippocampus was detectable at 4 days and remarkable at 7 days after reperfusion. 3. Coinciding with neuronal degeneration, ET-1- and ET-3-like immunoreactivities were intense in the CA1 pyramidal-cell layer, the stratum lacunosum moleculare, and the CA4 subfield of the hippocampus. Almost all of the immunostained cells had morphological characteristics of astrocytes. 4. The possibility that ET has a role in the development of neuronal cell death following transient forebrain ischemia warrants further attention.
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PMID:Increased production of endothelins in the hippocampus of stroke-prone spontaneously hypertensive rats following transient forebrain ischemia: histochemical evidence. 845 60

A novel experimental model of stroke has been developed using the powerful vasoconstrictor peptide, endothelin-1, to occlude the middle cerebral artery (MCA) of anaesthetised rats. Intracerebral microinjections of endothelin-1 were administered under stereotaxic guidance adjacent to the MCA, and after 3 days rats were perfusion fixed for histopathological determination of ischaemic brain damage. The pattern of brain damage noted using this model was similar to that reported following permanent surgical occlusion of the MCA. Brain damage was apparent in the dorsal and lateral neocortex (98 +/- 12 mm3) and striatum (32 +/- 3 mm3) ipsilateral to the insult. Rats anaesthetised with halothane and barbiturate exhibited a similar volume of brain damage. However, infarct volume increased when the duration of halothane anaesthesia was extended from 5 to 180 min post-occlusion. Neuroprotection studies demonstrated that dizocilpine (5 mg/kg, i.p.), administered 30 min prior to MCA occlusion, reduced the volume of cortical brain damage by 51% (P < 0.05) but did not alter the volume of striatal brain damage. The present results demonstrate that microinjections of endothelin-1 adjacent to the rat MCA result in a reproducible pattern of focal cerebral infarction which is sensitive to the duration of anaesthesia and can be reduced by dizocilpine.
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PMID:Characterisation of an experimental model of stroke produced by intracerebral microinjection of endothelin-1 adjacent to the rat middle cerebral artery. 854 71

1. We examined the effects of a selective endothelin A (ETA)-receptor antagonist, BQ-123, on the development of hypertension and organ damage in stroke-prone spontaneously hypertensive rats (SHRSP) given 1% NaCl for 6 weeks. 2. BQ-123 at doses of 0.7, 2.1 and 7.1 mg/day was continuously administered for 6 weeks to 8 week old salt-loaded SHRSP, who were given water containing 1% NaCl for the following 6 weeks, via a subcutaneous osmotic minipump. 3. Development of high blood pressure was accelerated in salt-loaded SHRSP compared with that in non-salt-loaded SHRSP. After 6 weeks of salt-loading, incidence of cerebral infarction, renal sclerosis and renal fibrosis were greater in salt-loaded than non-salt-loaded SHRSP. 4. BQ-123 attenuated the age-related rise in blood pressure in a dose-dependent manner. The effect coincided with reduction in the incidence of cerebral infarction and prevention of renal sclerosis and fibrosis. Kidney function was improved as observed by an increase in glomerular filtration rate and decreases in urinary protein excretion, blood urea nitrogen and fractional sodium excretion. Furthermore, BQ-123 prevented increases in the heart weight/bodyweight ratio and aortic wall thickness in salt-loaded SHRSP. 5. These results suggest that endogenous endothelin-1 (ET-1) and ETA-receptors may be, at least in part, involved in the pathogenesis of hypertension and organ damage in salt-loaded SHRSP.
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PMID:Effects of a selective endothelin A-receptor antagonist, BQ-123, in salt-loaded stroke-prone spontaneously hypertensive rats. 857 14

Plasma levels of endothelin-1 are elevated in patients with chronic heart failure; however, it is unknown whether changes in plasma endothelin-1 levels accurately reflect clinical response to therapy in these patients. To determine this, we measured plasma endothelin-1 in addition to functional, hemodynamic, and other neurohormonal parameters as part of a double-blind, placebo-controlled study of the beta-blocker vasodilator carvedilol in patients with moderate to severe chronic heart failure. Patients were assigned (2:1 randomization) to receive carvedilol (25 mg twice daily, n = 10) or placebo (n = 5) for 14 weeks, with evaluations made before and after therapy. Compared to patients receiving placebo, patients receiving carvedilol improved significantly as assessed by the parameters described. These changes were paralleled by significant falls in endothelin-1 with carvedilol (-2.1 + 3.8 pg/ml) in comparison to placebo (2.2 + 3.9 pg/ml; p < 0.05 for between-group differences). Changes in endothelin-1 after treatment in both groups correlated significantly with changes in symptom severity, New York Heart Association class, 6-minute walk distance (r = 0.64 to 0.80; p < 0.05), hemodynamic parameters (ejection fraction, right atrial pressure, pulmonary artery diastolic pressure, pulmonary wedge pressure, right atrial pressure, and stroke volume index; r = 0.54 to 0.86; p < 0.05), and neurohormonal parameters (serum aldosterone and plasma norepinephrine (r = 0.74 to 0.76; p < 0.05). By stepwise regression analysis, change in endothelin-1 was an independent, noninvasive predictor of functional and hemodynamic responses to therapy in these patients. These findings suggest that endothelin-1 accurately reflects functional, hemodynamic, and neurohormonal responses to beta-blocker therapy in patients with congestive heart failure. Measurement of endothelin-1 may therefore be a useful, noninvasive approach to the evaluation of clinical response to drug therapy in these patients.
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PMID:Changes in plasma endothelin-1 levels reflect clinical response to beta-blockade in chronic heart failure. 857 30

The effect of centrally administered endothelin-1 (ET-1) or IRL 1620 (5, 15, and 45 ng) on systemic hemodynamics was studied in anesthetized rats using a radioactive microsphere technique. Administration of saline (5 microliters, i.c.v.) did not product any significant cardiovascular effects. The lower doses of ET-1 (5 and 15 ng) did not produce any significant effect on blood pressure (BP), heart rate (HR), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR). However, the highest dose (45 ng) produced a transient rise followed by a sustained fall in BP. The CO and SV decreased significantly, whereas HR and TPR were not affected. Pretreatment with BQ-123 (10 micrograms, i.c.v.) 15 min before administration of ET-1, completely antagonized the systemic hemodynamic effects of ET-1. Centrally administered IRL 1620, a specific ETB receptor agonist, did not produce any effect on BP, HR, CO, SV, and TPR in rats. It is concluded that ETA but not ETB receptors are involved in the central cardiovascular actions of ET.
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PMID:Cardiovascular effects of centrally administered endothelin-1 in rats. 858 77


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