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)

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

Diaspirin cross-linked hemoglobin (DCLHb) is a promising hemoglobin-based, oxygen-carrying resuscitative solution. DCLHb (400 mg/kg, iv) produces significant cardiovascular effects, along with an increase in plasma endothelin-1 (ET-1) level, when administered to conscious or anesthetized rats. Present studies were performed to determine whether the cardiovascular effects of DCLHb are due to an increase in the conversion of proendothelin-1 (1-38) (proET-1) to ET-1 by endothelin-converting enzyme (ECE). The regional circulatory and systemic hemodynamic effects of proET-1 (20 micrograms/kg, iv) and DCLHb (400 mg/kg, iv) were determined by using a radioactive microsphere technique in control rats and rats pretreated with phosphoramidon (ECE inhibitor). Administration of proET-1 produced an immediate increase in mean arterial pressure (MAP)(52%) and total peripheral resistance (TPR) (55%); stroke volume (SV) and cardiac output were not affected in the initial phase but were decreased subsequently. Heart rate (HR) was not affected after administration of proET-1. A significant increase in blood flow to the heart (39%), brain (46%), kidneys (74%), portal system (40%), and gastrointestinal tract (GIT) (42%) was also observed after administration of proET-1. Vascular resistance was found to be significantly increased in the mesentery and pancreas (168%) and in the musculoskeletal system (147%) and decreased in the kidneys (-11%) after administration of proET-1. Phosphoramidon (4 mg/kg, iv) pretreatment attenuated the increase in MAP and TPR induced by proET-1. Phosphoramidon pretreatment significantly attenuated the proET-1-induced increase in blood flow to the heart, brain, kidneys, portal system, and GIT. The increase in vascular resistance induced by proET-1 in the mesentery and pancreas and in the musculoskeletal system was also attenuated by phosphoramidon. DCLHb increased MAP (63%) and TPR (54%) without affecting HR. DCLHb increased blood flow to the heart (95%), GIT (45%), portal system (43%), and skin (79%) and increased vascular resistance in the musculoskeletal system (58%). In phosphoramidon-treated rats, DCLHb increased MAP (99%), HR (25%), cardiac output (37%), and TPR (60%). DCLHb increased blood flow to the heart (104%), brain (66%), kidneys (49%), GIT (59%), portal system (63%), and skin (100%) when administered to phosphoramidon-treated rats. Phosphoramidon did not attenuate any of the DCLHb-induced cardiovascular effects. It is concluded that proET-1 increases blood flow to various organs and that phosphoramidon, an ECE inhibitor, could block the proET-1-induced increases in regional blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of endothelin-converting enzyme in the systemic hemodynamics and regional circulatory effects of proendothelin-1 (1-38) and diaspirin cross-linked hemoglobin in rats. 749 May 15

The purpose of these experiments was to compare the effects of endopeptidase inhibition with oral candoxatril on systemic and forearm hemodynamics and muscle sympathetic nerve activity with responses to a low-dose atrial natriuretic factor infusion. Eleven healthy men received at random on three separate days either intravenous saline, natriuretic factor (1.6 pmol/kg per minute) plus saline, or oral candoxatril (200 mg) plus saline. Measurements were made at baseline and 30, 60, and 90 minutes after interventions. Atrial natriuretic factor lowered diastolic pressure (P < .01), central venous pressure (P < .001), forearm blood flow (P < .05), and forearm vascular compliance (P < .05) but had no effect on systolic pressure, heart rate or its variability, stroke volume, sympathetic nerve activity, plasma norepinephrine, or endothelin-1. Plasma epinephrine increased (P < .01). Candoxatril lowered central venous pressure (P < .001) and increased systolic pressure (from 116 +/- 6 to 120 +/- 7 mm Hg; P < .05), endothelin (from 4.6 +/- 1.1 to 6.8 +/- 3.2 pmol/L; P < .02), and epinephrine (P < .05), without affecting any other variables. Candoxatril and atrial natriuretic factor lowered central venous pressure in healthy men without causing a reflex increase in sympathetic nerve activity or norepinephrine, yet epinephrine rose. This suggests that both interventions may specifically inhibit sympathetic nerve traffic to muscle at physiological plasma atrial natriuretic factor concentrations. However, whereas the peptide lowered blood pressure, candoxatril increased systolic pressure. These contrasting hemodynamic responses may be related to differences in plasma atrial natriuretic peptide concentration and to altered endothelin metabolism by candoxatril.
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PMID:Comparison of candoxatril and atrial natriuretic factor in healthy men. Effects on hemodynamics, sympathetic activity, heart rate variability, and endothelin. 749 88

Hypertension is a complex disease, the treatment of which should not only lower systolic and diastolic blood pressure but also attenuate the secondary consequences of the disease. These include vascular injury (including atherosclerosis), stroke, left ventricular hypertrophy, and renal damage. To establish whether the long-acting, vascular-selective calcium antagonist amlodipine attenuates some of these secondary consequences of hypertension, 5-week-old stroke-prone hypertensive and 8-week-old spontaneously hypertensive rats were treated (orally) with 5 mg/kg/day and 10 mg/kg/day amlodipine, respectively, for 30 weeks. The treatment resulted in a significant lowering of systolic blood pressure, accompanied by reduced cardiac hypertrophy and prolonged survival. Evidence for a protective effect of amlodipine on the vasculature was obtained by treating cholesterol-fed rabbits with 1-5 mg/kg/body weight/day. This resulted in a reduction in vascular Ca2+ overloading and a reduced incidence of sudanophilic lesion formation. Protection against ischemia-induced changes in the myocardium included a reduction in the ischemia-induced externalization of endothelin-1 binding sites.
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PMID:End-organ involvement and calcium antagonist therapy: animal studies. 760 72

We previously reported that the endothelin-1 (ET-1)-induced increase in microvascular permeability in isolated rat lungs required leukocytes in the perfusate. The present study examines whether intravenous administration of ET-1 in rats causes an inflammatory reaction in the lungs. Histological examination of the lung specimens 2 hr following ET-1 infusion showed adhesion of leukocytes to the vascular endothelium in pulmonary vessels and sequestration of leukocytes in the pulmonary capillaries. Microscopic examination of the bronchoalveolar lavage fluid revealed that leukocytes had migrated into the alveoli. Simultaneously a depletion of peripheral blood leukocytes was observed. These effects were reversible by 24 hr. Monitoring of systemic hemodynamic effects showed a continued reduced cardiac stroke volume and increasing heart rate after 2 hr. In isolated rat lungs, ET-1 caused a rapid increase in pulmonary artery pressure, pulmonary microvascular pressure, and edema formation. Compared with Krebs-albumin-perfused lungs, blood-perfusion accelerated the edemagenic effect of ET-1. ET-1 plays a role in the regulation of leukocyte-endothelial cell interactions in the pulmonary circulation. This has potential importance for the edemagenic effect of ET-1.
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PMID:Endothelin-1 causes accumulation of leukocytes in the pulmonary circulation. 762 62

The plasma levels of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) have been measured in 37 patients with acute ischemic stroke, on admission and 3 and 7 days thereafter. The plasma ET-1 levels at the onset of symptoms were about two-fold those observed in age-matched normal volunteers (3.5 +/- 2.26 v 1.54 +/- 0.9 pg/mL, respectively; P < .001). These levels remained significantly elevated during the 7-day study period. The neurologic deficit was assessed daily by Mathew's modified scale (MS). A significant correlation was found between neurologic status on admission and ET-1 plasma values; patients with worse neurologic status (MS < 45 points) had higher ET-1 plasma values than those with better neurologic status (MS > 45 points) (5.4 +/- 2.34 v 3.05 +/- 2.04 pg/mL, respectively, P < .05). The plasma ET-1 values did not correlate either with the site of the infarction or with its primary cause (cardioembolic, lacunar, or atherothrombotic). No significant differences were seen in plasma ET-1 concentrations between patients who eventually died and those who survived the acute event. The plasma ANP were about 18-fold higher in ischemic stroke patients on admission than in controls at admission (110.9 +/- 29.5 v 5.84 +/- 3.96 pg/mL, respectively, P < .01). These values remained significantly elevated on days 3 and 7. There was no correlation between the ANP plasma values and the neurologic status, the site or mechanism of the stroke, or the plasma ET-1 levels. In conclusion, ischemic stroke is associated with marked acute and long-duration increases of ET-1 and ANP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High plasma levels of endothelin-1 and atrial natriuretic peptide in patients with acute ischemic stroke. 770 3

Indirect evidence has implicated endothelin-1 in the pathogenesis of hypertension. In the present study we examined such a role directly with SB 209670, a novel nonpeptide endothelin receptor antagonist. The antihypertensive and hemodynamic effects of SB 209670 were examined in conscious, unrestrained spontaneously hypertensive (SHR), normotensive Wistar-Kyoto (WKY), and renin-hypertensive rats. Sustained intravenous infusion of SB 209670 (10 micrograms.kg-1.min-1 for 6 hours) produced a significant, reversible reduction in mean arterial pressure in SHR but not in WKY rats. The antihypertensive response to 10 micrograms.kg-1.min-1 SB 209670 (approximately 25 mm Hg reduction in blood pressure) was associated with bradycardia (16% decrease in heart rate) but only a minimal reduction (3%) in cardiac output, because stroke volume was evaluated (by 15%). Therefore, the antihypertensive effect of SB 209670 resulted from a decrease (13%) in total peripheral resistance. A sustained antihypertensive effect could also be observed after intraduodenal administration of SB 209670 (3 mg/kg) in conscious SHR (reduction of approximately 35 mm Hg 5 hours after administration). SB 209670 (3 mg/kg intravenous bolus) did not alter the pressor response or tachycardia observed in pithed SHR after stimulation of thoracolumbar sympathetic outflow. SB 209670 was also antihypertensive in renin-hypertensive rats, lowering blood pressure to an extent similar to that observed in SHR. Thus, the data presented provide evidence to support a role for endothelin-1 in the pathophysiology of two animal models of hypertension.
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PMID:Antihypertensive actions of the novel nonpeptide endothelin receptor antagonist SB 209670. 772 37

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 is a novel, potent, endogenous vasoconstrictor derived predominantly from endothelium and macrophages. Release of endothelin-1 (ET-1) into biological fluids was determined by radioimmunoassay in pigs undergoing either a hemorrhagic (3 h) or superior mesenteric artery (SMA) occlusion (5 h) shock followed by reperfusion (90 min) or a control group which was observed for 8 h. After surgery, there was a significant increase in ET-1 in jugular and carotid plasma, lymph, and ascitic fluid in all three models. The portal plasma ET-1 level was significantly increased (p < .05, assessed by the Spearman rank coefficient rho) in both shock models, but no significant increase was noted in the control group. In the SMA occlusion shock model, four pigs died within 30 min of reperfusion, and these animals had a much higher level of portal ET-1 (22.3 +/- 5.5 fmol/mL) than the two pigs that were alive by the end of the observation period (11.5 +/- 1.3 fmol/mL). Reperfusion in the SMA occlusion shock model induced a critical form of circulatory shock characterized by hypotension, decreased cardiac output, and decreased left and right ventricular stroke work index, and death occurred usually within 90 min. Reperfusion of the shed blood in the hemorrhagic shock model almost normalized the hemodynamic derangements caused by the hypovolemia (with the exception of RVSWI), and the portal plasma and ascitic ET-1 levels decreased. These results indicate that ET-1 is released from the gut in response to both general hypoperfusion and selective intestinal ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelin and hemodynamic responses to superior mesenteric artery occlusion shock and hemorrhagic shock in pigs. 774 37

In acute cerebral ischemia there are severe damages of endothelium recognized as the stimuli for secretion of endothelin-1, that is a endothelium-derived peptide and seems to be the most potent vasoconstrictor known. The goal of this study is to measure plasma endothelin-1 level in patients with cerebral infarction and determine the relationship between endothelin-1 and ischemic stroke. Plasma level of endothelin-1 was measured in 21 consecutive patients. The measurement was performed 3 times at different stages of stroke. There was a marked increase in plasma endothelin-1 level in the patients and the elevation lasted the entire acute and subacute stage of stroke. There was a correlation between the peptide concentration and infarct volume (r = 0.665, P < 0.01). The result suggests that endothelin-1 plays an important role in the regulation of brain circulation. Apparent and lasting increase in plasma level of endothelin-1 is associated with cerebral ischemia and infarction. The peptide seems to be involved in the pathophysiology of acute cerebral ischemia and have a deleterious effect in the evolution of cerebral infarction.
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PMID:[Increased plasma endothelin-1 concentration in acute cerebral infarction and its clinical significance]. 786 29


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