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

The vasodilation of pregnancy is thought by many to be due to increased endothelial production of prostacyclin, a vasodilatory prostanoid. Indomethacin, a potent inhibitor of prostaglandin synthesis, is known to increase the maternal blood pressure response to angiotensin II infusion. We sought to measure directly the hemodynamic effects of a short course of indomethacin. Twenty-three healthy pregnant women with uncomplicated pregnancies between 26-32 weeks' gestation completed the study. Using Doppler technology, we determined cardiac output, stroke volume, and total peripheral resistance before and after three 25-mg doses of indomethacin. Although blood pressure did not change, peripheral resistance rose and stroke volume fell following indomethacin administration. Our findings support the hypothesis that indomethacin interferes with tonic prostaglandin-induced vasodilation in pregnancy. However, the increase in vascular resistance was very slight, suggesting that other vasodilators are also at work in pregnancy. We recommend that indomethacin be used judiciously in hypertensive pregnant patients until more information concerning possible adverse hemodynamic effects becomes available.
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PMID:The maternal hemodynamic effect of indomethacin in normal pregnancy. 156 45

1. Measurements of changes in renal, mesenteric and hindquarters haemodynamics or cardiac haemodynamics in response to i.v. bolus doses of arginine vasopressin (AVP) or lysine vasopressin (LVP, 0.7 and 7.0 pmol) were made in conscious, chronically-instrumented Long Evans rats. 2. In some experiments AVP and LVP were administered during an infusion of NG-nitro-L-arginine methyl ester (L-NAME; 1.0 or 0.3 mg kg-1 h-1) to determine whether or not inhibition of nitric oxide production influenced the cardiovascular effects of the peptides. In other experiments, indomethacin (bolus dose of 5 mg kg-1 followed by infusion at 5 mg kg-1 h-1) was given to determine the possible involvement of cyclo-oxygenase products in the responses to AVP and LVP. 3. Under control conditions, the lower dose of LVP had significantly greater effects than AVP on heart rate, mean arterial blood pressure, renal, mesenteric and hindquarters conductances, total peripheral conductance, cardiac index, peak aortic flow and +dF/dtmax. The higher dose of LVP had significantly greater effects than AVP on all variables (i.e. including stroke index and central venous pressure). 4. In the presence of L-NAME (1 mg kg-1 h-1) there was a sustained increase in mean arterial blood pressure (+23 +/- 3 mmHg) and reductions in mesenteric (-38 +/- 4%) and hindquarters (-30 +/- 6%) vascular conductances. Under these conditions the difference in the pressor effects of AVP and LVP was abolished, but their differential effects on regional and cardiac haemodynamics persisted. This dose of L-NAME did not change cardiac baroreflex sensitivity. 5. During infusion of L-NAME at a lower rate (0.3mgkg-th-1), baseline cardiovascular status was unchanged and regional haemodynamic effects of AVP and LVP were enhanced, but the differences in the regional vasoconstrictor responses to the two peptides persisted. 6. Indomethacin (5 mg kg-1 bolus, then 5 mg kg- 'h-1 infusion) augmented the renal vasoconstrictor responses to AVP and LVP, but abolished the difference in the hindquarters vasoconstrictor responses to the two peptides. However, the differences in the pressor and the renal and mesenteric vasoconstrictor effects of AVP and LVP still occurred in the presence of indomethacin. 7. The results indicate that AVP normally has lesser cardiovascular effects than LVP but this difference does not seem to be due to more effective stimulation of nitric oxide-mediated or cyclo-oxygenase-dependent vasodilator mechanisms by AVP than LVP.
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PMID:Effects of NG-nitro-L-arginine methyl ester or indomethacin on differential regional and cardiac haemodynamic actions of arginine vasopressin and lysine vasopressin in conscious rats. 204 32

Using strips of human basilar arteries mounted in organ chambers to record isometric tension, we investigated vascular reactivity to thrombin and bradykinin. Both agents produced endothelium-dependent relaxation of basilar artery strips precontracted with phenylephrine but had no effect on resting tension in strips with or without endothelium. The relaxations caused by thrombin were abolished by antithrombin III/heparin, hirudin, and MD805. Thrombin but not bradykinin caused complete tachyphylaxis toward a second exposure. Indomethacin did not inhibit the relaxations induced by thrombin or bradykinin, whereas bromophenacyl bromide and methylene blue did. Aging decreased the relaxation induced by thrombin but did not affect the concentration needed to reach 50% maximal relaxation, nor did it affect the maximal relaxation in response to bradykinin, calcium ionophore A23187, and sodium nitroprusside. Our results suggest that thrombin and bradykinin produce endothelium-dependent relaxations mediated by an endothelium-derived relaxing substance and that the relaxation caused by thrombin is mediated by a proteolytic action on endothelial cells. The decrease in relaxations in response to thrombin with increasing age might be due to a decrease in the number or sensitivity of thrombin receptors on endothelial cells.
Stroke 1990 Jul
PMID:Effect of aging on endothelium-dependent vascular relaxation of isolated human basilar artery to thrombin and bradykinin. 211 73

We studied the effects of acetylcholine and calcium ionophore A23187 on human basilar artery rings. Among 11 arteries, both agents produced significant relaxations in five, A23187 but not acetylcholine caused a response in six, and neither agent was effective in four. After rubbing off the endothelium, the relaxations induced by both agents were significantly attenuated. Indomethacin (a cyclooxygenase inhibitor) and AA861 (a specific inhibitor of 5-lipoxygenase) did not but SKF525A (an inhibitor of cytochrome P450-dependent monooxygenase) did significantly inhibit the acetylcholine-induced relaxation in human basilar arteries. On the other hand, AA861 inhibited while neither indomethacin nor SKF525A had any effect on the A23187-induced relaxation. Our results suggest that different mechanisms may be involved in acetylcholine and A23187-induced relaxations in human basilar arteries.
Stroke 1989 Sep
PMID:Endothelium-dependent relaxation of human basilar arteries. 250 8

We induced brain edema in 72 rats by injecting 5 microliters of 3.0% wt:vol polyvinyl acetate into the left internal carotid artery, producing permanent embolization in the left cerebral hemisphere, which developed ipsilateral brain edema reproducibly. Edema was assessed 24 hours after embolization by determining the brain water content and the sodium and potassium concentrations. In this model, the free radical scavenger MCI-186 at 1.0 and 3.0 mg/kg i.v. prevented brain edema in a dose-dependent manner. At 3.0 mg/kg i.v., MCI-186 significantly reduced water content by 1.5% and improved the sodium-potassium balance to within the normal range in the embolized left hemisphere. Dexamethasone at 1.0 mg/kg i.v. did but at 3.0 mg/kg i.v. did not significantly inhibit the development of brain edema. Indomethacin at 4.0 mg/kg i.p. had no effect on brain edema. We suggest that the cyclooxygenase metabolites of arachidonic acid liberated from neuronal cell membrane phospholipids are not likely to be involved in the pathogenesis of permanent brain edema induced by polyvinyl acetate. Our results suggest that MCI-186 attenuates brain edema by suppressing the production of lipoxygenase metabolites, including free radicals or lipid peroxides, and that it may prove valuable for the treatment of brain edema associated with cerebral ischemia.
Stroke 1989 Sep
PMID:Effect of MCI-186 on brain edema in rats. 250 9

Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups. We compared local cerebral blood flow and cortical specific gravity between the PI and RC subgroups of the control and drug-treated groups. In the PI subgroup, indomethacin did not influence the time course of local cerebral blood flow but significantly worsened the decrease in cortical specific gravity. On the other hand, indomethacin significantly improved postischemic hypoperfusion and ameliorated the decrease in cortical specific gravity in the RC subgroup. The effects of ONO-3144 were similar to those of indomethacin, except that ONO-3144 did not affect cortical specific gravity in the PI subgroup. Indomethacin inhibits cyclooxygenase activity, whereas ONO-3144 scavenges the oxygen-centered radical released in the conversion of prostaglandin G2 to prostaglandin H2. Thus, prostaglandins do not seem to play a major role in the occurrence of brain edema due to prolonged regional ischemia. By contrast, oxygen-centered radicals released from the cyclooxygenase pathway appear to be at least partially responsible for the occurrence of recirculation-induced edema and postischemic hypoperfusion.
Stroke 1989 Jun
PMID:Effect of indomethacin and a free radical scavenger on cerebral blood flow and edema after cerebral artery occlusion in cats. 272 47

The effects of mannitol, nimodipine, and indomethacin on ischemic neuronal injury were examined in 45 rats divided equally into nine groups subjected to 10 minutes of forebrain ischemia. Of two control groups, one received maintenance fluids while the other received a normal saline bolus. In the remaining seven groups, mannitol, nimodipine, and indomethacin were administered singly or in combination 5 minutes before forebrain ischemia. Seven days after ischemia, the brains were perfusion-fixed, sectioned coronally into 2.8-mm slices, and stained with hematoxylin and eosin. Ischemic neurons were directly counted on predetermined regions of standardized serial sections. Considerable amelioration of ischemic injury (ischemic neurons/total neurons) was observed with mannitol (ischemic injury, 7 +/- 5% in the hippocampal CA1/CA2 sectors and 28 +/- 17% in the CA3 sector). This is in contrast to control values of 64 +/- 11% and 80 +/- 6%, respectively, and those obtained in the normal saline group of 70 +/- 10% and 59 +/- 13%, respectively. The beneficial effect with nimodipine reached significance in only the hippocampal CA3 sector (ischemic injury, 35 +/- 21%). Indomethacin showed no significant benefit. Combining the agents resulted in significantly reduced neuronal injury compared with control groups, although the effect was not greater than that achieved with mannitol alone. The degree of ischemic injury was least when all three agents were used in combination (ischemic injury, 12 +/- 12% in the hippocampal CA1/CA2 sectors and 4 +/- 4% in the CA3 sector). Our data support the concept that successfully blocking the ischemic cascade with a single, diversely acting agent or multiple agents will evoke the best beneficial response.
Stroke 1988 May
PMID:Effect of mannitol, nimodipine, and indomethacin singly or in combination on cerebral ischemia in rats. 312 27

The purpose of our experiment was to examine whether the cyclooxygenase inhibitor indomethacin ameliorates neuronal injury in the gerbil hippocampal CA1 sector following 5 minutes of forebrain ischemia. Thirty minutes before bilateral carotid artery occlusion, Mongolian gerbils were injected intraperitoneally with 1 (n = 10), 2 (n = 10), 5 (n = 12), or 10 (n = 7) mg/kg of indomethacin. Seven days after occlusion, the gerbils were perfusion-fixed and neuronal density in the hippocampal CA1 sector was assessed. The mean +/- SEM neuronal density in nine unoperated normal gerbils was 307 +/- 9/mm, in 10 untreated ischemic gerbils 55 +/- 21/mm, and in seven vehicle-treated ischemic gerbils 15 +/- 9/mm. The mean +/- SEM neuronal density in ischemic gerbils treated with 1, 2, 5, or 10 mg/kg indomethacin was 132 +/- 28/mm, 154 +/- 29/mm, 176 +/- 30/mm, and 136 +/- 39/mm, respectively. Indomethacin at any dose significantly ameliorated ischemic neuronal damage in the gerbil hippocampal CA1 sector.
Stroke 1988 Nov
PMID:Indomethacin ameliorates ischemic neuronal damage in the gerbil hippocampal CA1 sector. 318 24

The goal of this study was to determine whether responses of cerebral arterioles to products released by platelets are impaired in stroke-prone spontaneously hypertensive rats (SHRSP). The diameter of pial arterioles was measured during suffusion with adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue U-46619, using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and SHRSP (7-10 months old). Responses of cerebral arterioles to ADP and serotonin were profoundly impaired in SHRSP. ADP (10(-5) M) increased pial arteriolar diameter 17 +/- 3% (mean +/- SE) in WKY and only 4 +/- 1% in SHRSP. Serotonin (10(-5) M) increased pial arteriolar diameter 15 +/- 2% in WKY and, in contrast, reduced the diameter 13 +/- 1% in SHRSP. Nitroglycerin produced a similar dilatation of cerebral arterioles in WKY and SHRSP, suggesting that impairment of dilatation in SHRSP in response to ADP and serotonin was not related to nonspecific impairment of vasodilatation in SHRSP. The thromboxane analogue U-46619 produced a similar constriction of arterioles in WKY and SHRSP. We also examined the possibility that impaired dilator responses of cerebral arterioles in SHRSP in response to ADP and serotonin may be related to production of a cyclooxygenase vasoconstrictor substance. Indomethacin (10 mg/kg i.v.) partially restored dilator responses to ADP and serotonin in SHRSP, without altering responses in WKY. Thus, we speculate that vasoactive substances released by platelets may release a prostanoid constrictor substance from cerebral vessels of SHRSP and thereby predispose SHRSP to cerebral ischemia and, perhaps, stroke.
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PMID:Responses of cerebral arterioles to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619 during chronic hypertension. 320 60

The involvements of arachidonic acid metabolites in the development of ischemic brain edema and cerebral energy metabolism were investigated on the experimental ischemia and reperfusion model. The level of arachidonic acid in brain tissue increases especially on the ischemic insult, which is rapidly converted to prostaglandins and leukotrienes after the reperfusion. The drugs which modify the arachidonic acid metabolism were administrated to clarify the effect on ischemic brain edema and cerebral energy metabolism. Male stroke resistant spontaneously hypertensive rats (SHRSR) were subjected to incomplete ischemia for two hours by occlusion of both common carotid arteries with vascular clips, and reperfused for two hours. The drugs used are dexamethasone, indomethacin, trapidil and OKY-046. Indomethacin inhibits cyclooxygenase. Dexamethasone inhibits phospholipases by the production of lipocortin. OKY-046 inhibits thromboxane A2 synthetase. Trapidil inhibits thromboxane A2 synthetase and increases the level of 6-keto-PGF1 alpha. These drugs were administered 18 hours before, just after clipping on (1/2) and off (1/2). Brain water content, cerebral ATP and lactic acid levels were examined. In the saline treated group, the cerebral water content was increased after the reperfusion and reached its maximal level after two hours of the reperfusion. The development of brain edema was prevented by the administration of dexamethasone or trapidil, but not by indomethacin and OKY-046. Administration of trapidil or dexamethasone was found to prevent the decrease in ATP and the increase of lactic acid. In the indomethacin administrated group, only the increase of lactic acid was prevented. 6-keto-PGF1 alpha was high in the trapidil administrated group and low in the indomethacin administrated group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Involvement of arachidonic acid cascade in brain edema and cerebral energy metabolism after reperfusion]. 359 3


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