Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 and/or -2(ET1 + 2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1 + 2 from cultured endothelial cells in a dose-dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1 + 2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol-induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome.
 ...
PMID:Ethanol stimulates immunoreactive endothelin-1 and -2 release from cultured human umbilical vein endothelial cells. 159 May 57

The hemodynamic effect of human-porcine endothelin (endothelin-1, ET-1) and rat endothelin (endothelin-3, ET-3) administration into conscious male, Sprague-Dawley rats was investigated. Bolus administration of ET-1 produced sustained, dose-dependent increases in mean arterial pressure (MAP) and total peripheral resistance (TPR). ET-1 also produced dose-dependent decreases in cardiac output (CO) and heart rate (HR), although dose-dependent changes in stroke volume (SV) were not observed. Similar results were obtained with 1-h infusions of ET-1. Infusions of ET-1 produced dose-dependent elevations in MAP that were sustained throughout the infusion period and for 1 h thereafter. TPR, CO, and HR were significantly altered only by the highest infusion rate of ET-1, whereas SV was not significantly affected by any rate of infusion of the peptide. These data indicate that ET-1 produces an overall dose-dependent increase in MAP through a mechanism involving an unusually prolonged increase in TPR. Similar experiments using ET-3 indicate that this sequence, acting through a mechanism similar to that of ET-1, may be metabolized more quickly, since the duration of its blood pressure effect is shorter than that of ET-1. Furthermore, in contrast to ET-1, ET-3 did not decrease HR and CO. The two peptide sequences do, however, appear to be equally efficacious as pressor agents, since the maximal change in MAP and time of onset of the maximal change in MAP induced by either peptide sequence are statistically comparable.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hemodynamic effect of human and rat endothelin administration into conscious rats. 217 45

Previous work has shown that the plasma levels of the potent vasoactive peptide endothelin (ET) are increased in pathophysiological conditions with increased pulmonary vascular resistance and it has been speculated that ET may play some part in hypoxic pulmonary hypertension. We have therefore evaluated the effects of ET-infusion in the porcine pulmonary circulation after hypoxia-induced hypertension. Pits under general anaesthesia were artificially ventilated through an endotracheal tube and hypoxia was induced by decreasing the fraction inhaled O2 from 0.21 to 0.10. Haemodynamic parameters were continuously recorded using a Swan-Ganz catheter in combination with thermodilution for cardiac output measurements. ET-1 or ET-3 was given as an i.v. infusion through the Swan-Ganz catheter in the right ventricle. Hypoxia induced a reproducible increase in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP) and right ventricular stroke work (RVSW) while the systemic vascular resistance (SVR) slightly decreased. Cumulative infusion of ET-1 (10, 25 and 50 ng kg-1 min-1) dose-dependently decreased MPAP and PVR; at a higher dose (100 ng kg-1 min-1), the PVR returned to the level observed at hypoxia. ET-infusions at 50 and 100 ng kg-1 min-1 evoked an increase in SVR and a decrease in cardiac output (CO) and stroke volume (SV). RVSW also gradually decreased during ET-1 infusion. Infusion of ET-3 evoked effects similar to those of ET-1 infusions, although the response to ET-3 was not that rapid in onset. In a second series of animals, repeated 15 min periods of hypoxia evoked a stable, reproducible response with a consistent increase in PVR, MPAP and RVSW which returned to baseline values during normoxia. Infusion of ET-1 (25 ng kg-1 min-1) evoked a rapidly developing decrease in PVR and MPAP which was quickly normalized upon cessation of the ET-infusion. ET-1 infusion at this concentration did not per se influence the haemodynamic parameters during normoxia. It is concluded that in the pig, short-term ET-infusion reduces the pulmonary hypertension associated with acute hypoxia.
 ...
PMID:Endothelin infusion reduces hypoxic pulmonary hypertension in pigs in vivo. 748 75

Central endothelin (ET) has been implicated in the regulation of the cardiovascular system. The effect of intracerebroventricular (i.c.v.) administration of ET-1 or IRL 1620 (5, 15 and 45 ng) on the systemic hemodynamics and regional circulation was studied in anesthetized rats using a radioactive microsphere technique. Systemic hemodynamics and regional blood circulation were determined before (baseline) and at 30 min after the injection of each dose of ET-1 or IRL 1620. Administration of saline (5 microliters, i.c.v.) did not produce 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), total peripheral resistance (TPR) and regional blood circulation. However, the higher dose (45 ng) produced a transient rise (26%) followed by a sustained fall (48%) in BP. The decrease in BP was accompanied by significant decreases in CO (44%) and SV (39%), while HR and TPR were not affected. ET-1 (45 ng, i.c.v.) also produced a significant reduction in blood flow to the brain (75%), heart (49%), kidneys (66%), GIT (40%), portal system (52%) and musculo-skeletal system (38%), while blood flow to the skin was not affected. To determine pharmacological specificity of the central effects of ET-1, studies were performed in rats pretreated with BQ-123, a specific ETA receptor antagonist. Pretreatment with BQ-123 (10 micrograms, i.c.v.), 15 min prior to the administration of ET-1, completely antagonized the systemic hemodynamic as well as the regional circulatory effects of ET-1 (45 ng, i.c.v.). In order to determine whether stimulation of central ETB receptors produces any cardiovascular effects, studies were performed using IRL 1620, a specific ETB receptor agonist. Administration of IRL 1620 (5, 15 and 45 ng, i.c.v.) did not produce any effect on systemic hemodynamics and regional blood circulation in rats. It is concluded that ETA but not ETB receptors are involved in the central cardiovascular actions of ET.
 ...
PMID:Systemic hemodynamic and regional circulatory effects of centrally administered endothelin-1 are mediated through ETA receptors. 779 63

We examined endothelin (ET) receptors in the hippocampus CA1 subfields of stroke-prone spontaneously hypertensive rats subjected to a 10-min bilateral carotid occlusion and reperfusion. When delayed neuronal death had occurred in the pyramidal cell layer at 7 days after transient forebrain ischemia, the quantitative receptor autoradiographic method we used revealed a dramatic increase in number of 125I-ET-1 binding sites in the hippocampus CA1 subfields. The highest number of de novo binding sites appeared in the area corresponding anatomically to the pyramidal cell layer with neuronal death. These binding sites were characteristically the ETB receptor. The de novo 125I-ET-1 binding was mainly present on microglia aggregating with a high density in the damaged pyramidal cell layer. As ET-1- and ET-3-like immunoreactivities were highly expressed within astrocytes in damaged neural tissue, the possibility that microglia with the ETB receptor are activated to participate in the pathophysiology of ischemia-related neural tissue damage by astrocytic ET-1 and ET-3 produced in response to transient forebrain ischemia would have to be considered.
 ...
PMID:Microglia with an endothelin ETB receptor aggregate in rat hippocampus CA1 subfields following transient forebrain ischemia. 805 45

An extremely potent and highly specific non-peptide, subnanomolar endothelin (ET) receptor antagonist, SB 209670, has been synthesized and characterized. SB 209670, which was rationally designed using conformational models of ET-1, selectively inhibits binding of 125I-labeled ET-1 to cloned human ET receptor subtypes ETA and ETB (Ki = 0.2 and 18 nM, respectively). SB 209670 produces concentration-dependent inhibition of ET-1-mediated vasoconstriction in isolated vascular tissues and in vivo following either intravenous or intraduodenal administration. SB 209670 produces a dose-dependent reduction in blood pressure in hypertensive rats, protects from ischemia-induced neuronal degeneration in a gerbil stroke model, and attenuates neointima formation following rat carotid artery balloon angioplasty. SB 209670 will be useful in characterizing and classifying the physiological and pathophysiological effects of ET.
 ...
PMID:SB 209670, a rationally designed potent nonpeptide endothelin receptor antagonist. 805 55

A newly synthesized ET(A)-selective antagonist, BQ-123, was examined with respect to its anti-endothelin(ET) action in vitro and in vivo and its effect on blood pressure in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP). In isolated porcine coronary arteries, BQ-123 (0.07 microM to 6.0 microM) shifted the concentration-response curve for ET-1 to the right without affecting the maximal response of ET-1, its pA2 value being 7.35. Intravenous infusion of BQ-123 at a rate of 1.2 and 30 mg/kg/hr produced a significant decrease in blood pressure in 20- to 29-week-old SHRSP, but did not alter blood pressure in 13- to 16-week-old WKY or in 18- to 19-week-old and 40-week-old SHR. The hypotensive effect of BQ-123 depended on the pretreatment blood pressure level. These results suggest that ET-1 is involved in part in the maintenance of high blood pressure in malignant hypertension, as exemplified by SHRSP.
 ...
PMID:Antihypertensive effect of a newly synthesized endothelin antagonist, BQ-123, in a genetic hypertensive model. 844 1

The endothelinB (ETB) receptor is involved in endothelin-induced vasoconstriction and appears to play a role in ET-induced positive inotropy. Our previous study could not detect a positive inotropic effect of ET-1 in vivo. To evaluate specifically the effects of the ETB receptor on hemodynamics and inotropy of ET-1 in the intact circulation, we examined in the open-chest rat model the dose-dependent hemodynamic and inotropic effects of the highly specific ETB agonist IRL 1620 (0.4, 1.0, 2.0, and 4.0 nmol/kg vs. NaCl controls) during and after a 7-min infusion. In addition to measurements in the intact circulation, isovolumic recordings (peak LVSP, peak dP/dtmax) were performed for quantification of myocardial contractility independently of peripheral vascular changes. IRL 1620 caused a significant biphasic blood pressure response with an initial fall and a sustained increase, reflecting the vasoactive effects of IRL 1620, with a transient vasorelaxation followed by dose-dependent and long-lasting vasoconstriction. Although IRL 1620 has a positive chronotropic effect the reduction in stroke volume (probably due to the elevated afterload) causes a decrease in cardiac output. Nevertheless, the isovolumic measurements indicate a significant positive inotropic effect of IRL 1620. Therefore, the selective activation of ETB receptors causes a positive inotropic effect, which is also detectable in vivo, as the vasoconstrictor and coronary constrictor effects are less pronounced compared to activation of both ETA and ETB receptors by ET-1.
 ...
PMID:In vivo hemodynamic and inotropic effects of the endothelinB agonist IRL 1620. 858 59

Intracerebroventricular (i.c.v.) injection of endothelin-1 (ET-1; 100 ng. i.c.v.) produced an initial pressor (24%) (peak at 3 min following ET-1 administration) and a delayed depressor (-40%) (30 and 60 min following ET-1 administration) effects in urethane anesthetized rats. The pressor effect of ET-1 was due to an increase (21%) in cardiac output, while the depressor effect of ET-1 was associated with a marked decrease (-46%) in cardiac output. Stroke volume significantly decreased at 30 and 60 min after the administration of ET-1. No change in total peripheral vascular resistance and heart rate was observed following central administration of ET-1. The effects of ET-1 on Blood pressure, cardiac output and stroke volume were not observed in BQ123 (10 micrograms, i.c.v.) treated rats. Blood flow to the cerebral hemispheres, cerebellum, midbrain and brain stem was not affected at 3 min, but a significant decrease in blood flow to all the regions of the brain was observed at 30 and 60 min following central administration of ET-1. BQ123 pretreatment completely blocked the central ET-1 induced decrease in blood flow to the brain regions. It is concluded that the pressor effect of centrally administered ET-1 is not accompanied by a severe decrease in brain blood flow, however, a subsequent decrease in blood pressure is associated with a decrease in blood flow to the brain. The cardiovascular effects of ET-1 including decrease in brain blood flow are mediated through central ET receptors.
 ...
PMID:Cardiovascular effects of centrally administered endothelin-1 and its relationship to changes in cerebral blood flow. 859 9

Big endothelin-1 (Big ET-1) was given intravenously to six healthy men to study uptakes and vascular effects. Blood samples were taken from systemic and pulmonary arterial and internal jugular and deep forearm venous catheters. Arterial Big ET-1-like immunoreactivity (Big ET-1-LI) increased from 5.43 +/- 0.60 to 756 +/- 27 pmol/l, and ET-1-LI increased from 4.67 +/- 0.08 to 6.67 +/- 0.52 pmol/l (P < 0.001). Skeletal muscle fractional extraction of Big ET-1-LI was 15 +/- 4%. ET-1-LI release did not increase in the studied vascular beds. Heart rate fell by 17% (P < 0.001), cardiac output fell by 26% (P < 0.001), and stroke volume fell by 11% (P < 0.05). Mean arterial blood pressure increased 18%, systemic vascular resistance increased 65%, and pulmonary vascular resistance increased 57% (P < 0.01-0.001). Pulmonary blood pressures, forearm blood flow, arterial pH, arterial PCO2, and systemic arterial-internal jugular venous O2 difference remained unchanged. No specific Big ET-1 receptors were found in human pulmonary membranes. The half-maximal inhibitory concentration for the receptor antagonist bosentan was 181 nM. In summary, circulating Big ET-1 elicits greater increases in mean arterial blood pressure and systemic vascular resistance and decreases in heart rate and cardiac output compared with an equimolar ET-1 infusion (26).
 ...
PMID:Central and regional hemodynamic effects during infusion of Big endothelin-1 in healthy humans. 880 95


1 2 3 4 5 6 7 8 Next >>