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

1. The cardiovascular effects of SRT6b in control and BQ-123, a specific ETA receptor antagonist, pretreated rats were determined in anesthetized rats using a radioactive microsphere technique. 2. Infusion of SRT6b produced an increase in blood pressure and total peripheral resistance, decrease in cardiac output and stroke volume, and no change in heart rate of control or BQ-123 treated rats. 3. SRT6b induced a decrease in blood flow to the heart which was completely blocked by BQ-123 pretreatment. The decrease in blood flow to other organs by SRT6b was not affected by BQ-123 pretreatment. 4. This study indicates that ET receptors in the coronary blood vessels are of a different type (neither ETA nor ETB) to those in other vascular beds.
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PMID:Endothelin ETA receptor antagonist, BQ-123, blocks the vasoconstriction induced by sarafotoxin 6b in the heart but not in other vascular beds. 771 59

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.
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PMID:Systemic hemodynamic and regional circulatory effects of centrally administered endothelin-1 are mediated through ETA receptors. 779 63

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

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.
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PMID:SB 209670, a rationally designed potent nonpeptide endothelin receptor antagonist. 805 55

The cardiovascular consequences of endothelin (ET) blockade with the ETA-receptor antagonist FR 139317 were evaluated by determining the long-term effects of the drug on hemodynamic, hormonal, renal and structural parameters in stroke-prone spontaneously hypertensive rats (SHR-SP). Young SHR-SP on a high-sodium diet develop malignant hypertension accompanied by renovascular and cerebrovascular lesions. In control SHR-SP the systolic blood pressure increased from 196 +/- 3 to 260 +/- 4 mm Hg, whereas in animals treated with FR 139317 (20 mg/kg intraperitoneally, twice daily) it increased only from 196 +/- 4 to 212 +/- 3 mm Hg during a treatment period of 6 weeks. There was also an increase in heart weight. At the end of the experiment the plasma levels of atrial natriuretic peptide and brain natriuretic peptide were significantly lower in the group treated with FR 139317 than in the controls. The endothelin plasma levels were significantly higher and the plasma renin activity was lower in the group treated with the endothelin receptor antagonist. These data indicate that endothelin is involved in the maintenance of high blood pressure and cardiac hypertrophy in malignant hypertension, as exemplified by SHR-SP.
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PMID:Prolonged endothelin blockade prevents hypertension and cardiac hypertrophy in stroke-prone spontaneously hypertensive rats. 855 37

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.
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PMID:In vivo hemodynamic and inotropic effects of the endothelinB agonist IRL 1620. 858 59

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

Previously, we demonstrated that cerebral focal ischemic tissue exhibits a significant increase in immunoreactive endothelin (ET). Because increased ET might exacerbate the consequences of cerebral ischemia, we evaluated the effects of the orally active ETA/B receptor antagonist SB 217242 on middle cerebral artery occlusion (MCAO) in the spontaneously hypertensive rat (SHR). SHRs were treated b.i.d. with vehicle or with 3 or 15 mg/kg SB 217242 p.o. for 7 days. Permanent MCAO was performed on day 7 and animals were sacrificed on day 8. Forebrains were stained and the extent of cerebral (i.e., cortical) infarction was determined using image analysis. Hemispheric swelling (%), hemispheric infarct (%), and infarct volume (mm3) were quantitated for each animal. SB 217242 treatment produced a significant decrease in ischemic brain injury. Hemispheric infarction and infarct volume were reduced after the 15 mg/kg treatment (12.0 +/- 1.1% and 69 +/- 6 mm3) compared to vehicle (17.3 +/- 1.5% and 99 +/- 8 mm3) (p < 0.05). No significant effects on hemispheric swelling were observed. This is the first demonstration of an ET receptor antagonist exhibiting efficacy in cerebral focal ischemia. The fact that a 30% reduction in ischemic brain injury can be demonstrated after oral administration of SB 217242 suggests that ET antagonists may be of therapeutic utility in focal stroke.
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PMID:The endothelin receptor antagonist SB 217242 reduces cerebral focal ischemic brain injury. 858 28

The cardiovascular consequences of endothelin (ET) blockade with the ETA receptor antagonist FR 139317 were evaluated by determining long-term effects of the drug on hemodynamic, hormonal, and structural parameters in stroke-prone spontaneously hypertensive rats (SHR-SP). Young SHR-SP on a high-sodium diet develop malignant hypertension accompanied by renovascular and cerebrovascular lesions. In control SHR-SPs the systolic blood pressure increased from 196 +/- 3 to 260 +/- 4 mm Hg, whereas in animals treated with FR 139317 (20 mg/kg, i.p., b.i.d.) blood pressure increased only from 196 +/- 4 to 212 +/- 3 mm Hg during a treatment period of 6 weeks. The increase in heart weight was also delayed. At the end of the experiment, the plasma levels of ANP and BNP were significantly lower in the group treated with FR 139317 than in the controls. The plasma ET levels were significantly higher and the plasma renin activity was lower in the group treated with the ET receptor antagonist. These data indicate that ET is involved in the maintenance of high blood pressure and cardiac hypertrophy in malignant hypertension, as exemplified by an SHR-SP rat model.
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PMID:Prolonged endothelin blockade reduces hypertension and cardiac hypertrophy in SHR-SP. 858 37

The role of endothelin-1 (ET-1) in the development and maintenance of hypertension is controversial. To determine the role of ET-1, we investigated the possible involvement of ET-1 in the pathogenesis of experimental hypertensive rats. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a significant increase in aortic immunoreactive ET (IR-ET) level was observed, compared with age-matched sham-operated rats. Intravenous injection of the ETA receptor antagonist FR139317 (10 mg/kg) produced a slight decrease in blood pressure in sham rats. In the DOCA-salt hypertensive rats, FR139317 had a more pronounced hypotensive effect. Treatment with the antagonist in nitro-L-arginine (LNA)-induced hypertensive rats, two-kidney, one-clip (2K1C) renal hypertensive rats, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHR-SP) produced only moderate hypotensive effects, of the same degree as those in normotensive rats. Long-term treatment with FR139317 in DOCA-salt hypertensive rats efficiently suppressed the development of hypertension and cardiovascular hypertrophy. We propose that ET-1 production in vascular tissues is increased in DOCA-salt hypertensive rats. In addition, our study suggests the pathophysiologic importance of ET-1 and the ETA receptor in DOCA-salt-induced hypertension but not in SHR, in SHR-SP, in 2K1C renal hypertension, and in LNA-induced hypertension.
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PMID:Involvement of endothelin-1 in deoxycorticosterone acetate-salt-induced hypertension and cardiovascular hypertrophy. 858 44


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