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

The hemolysate (10(-5)-10(-2) times dilution; original hemoglobin concentration was 0.83 +/- 0.10 X 10(-3)M) evoked the contraction in a dose dependent manner, and this contraction was composed of low and high sensitive responses as estimated from the Eadie-Hofstee's plot. Indomethacin (10(-7)-10(-5)M) inhibited the latter component in the hemolysate-induced contraction. The membrane potential of smooth muscle cells was -50 mV and the cell was electrically quiescent. The hemolysate (greater than 10(-2) times dilution) depolarized the membrane and increased the ionic conductance of membrane. In rare occasions, the spike potential was triggered on the hemolysate-induced depolarization. The hemolysate (10(-5)-3 X 10(-3) times dilution) produced the contraction with no change in the membrane property. Carbocyclic thromboxane A2 ( cTXA2 ; 2.8 X 10(-10)M) produced the contraction without depolarization of the membrane, yet the TXA2 synthesis inhibitor, OKY-1581 (10(-5)M), had no effect on the hemolysate-induced contraction. PGE1, PGE2 and PGF2 alpha (2.8 X 10(-6)M) produced the contraction with no change in the membrane property. The contraction evoked by 2.8 X 10(-6)M PGF2 alpha corresponded well with that evoked by 3 X 10(-3) times dilution of the hemolysate. Removal of the endothelium by mechanical rubbing modified the hemolysate-induced contraction. Under the assumption that OKY-1581 is a selective inhibitor for TXA2 synthesis, the major part of the contraction (the indomethacin sensitive component) of the basilar artery is postulated to be due to synthesis of the primary PG rather than TXA2 by the hemolysate, yet the hemolysate itself, has to some extent a direct action in evoking the small contraction.
Stroke
PMID:Hemolysate-induced contraction in smooth muscle cells of the guinea pig basilar artery. 672 80

We examined whether endogenous prostaglandins (PGs) participated in control of hindquarters vascular resistance during salt loading in stroke-prone spontaneously hypertensive rates (SHR-SP). SHR-SP and Wistar-Kyoto rats (WKY) were fed either a normal (0.3% NaCl) or high (8% NaCl) salt diet for 5 wk. High salt increased blood pressure and hindquarter vascular resistance (VR) in SHR-SP (P less than 0.01) but not in WKY. Indomethacin given intravenously increased hindquarter VR in SHR-SP during high salt as well as during normal salt (P less than 0.01) but not in either group of WKY. In SHR-SP the increase in hindquarter VR by PG synthesis inhibitors were two times greater during high salt than during normal salt (P less than 0.01). In addition, hindquarter vasodilatation by bradykinin was greater (P less than 0.05) in SHR-SP during high salt than that during normal salt, but vasodilatation by prostaglandin E1 or nitroglycerin was not different between the two groups. These results suggest that vascular synthesis of endogenous PGs was greater in SHR-SP during high salt than that during normal salt. Increased endogenous PGs may play an important role in the regulation of hindquarter VR during high salt intake in SHR-SP.
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PMID:Salt loading augments vascular responses to indomethacin in stroke-prone SHR. 681 Jul 12

Systemic hemodynamics and blood flow were measured in conscious beagle dogs treated with the nonsteroidal antiinflammatory agent indomethacin. Twenty minutes after 2 mg/kg of indomethacin i.v., mean arterial blood pressure increased 5%, but cardiac output fell 24%, due to a decline in heart rate (-10%) and stroke volume (-18%). Small nonsignificant reductions in total bone, coronary, spleen, renal, and brain blood flow paralleled this fall in cardiac output. Larger, statistically significant reductions in arterial perfusion were seen in the skin (-30%), stomach (-47%), and small intestine (-27%). The corresponding 83, 101, and 38% increases in vascular resistance in these tissue beds largely accounted for the 41% increase in total peripheral resistance with indomethacin. Vascular resistance increased slightly in the vehicle control group due to reduced skeletal muscle blood flow seen in both treatment groups. Ovarian and thyroid blood flow also decreased with indomethacin. Indomethacin thus exerts a relatively specific vasoconstriction in the skin and upper gastrointestinal tract of the conscious dog.
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PMID:The effects of indomethacin on systemic hemodynamics and blood flow in the conscious dog. 684 43

1. In basal conditions, plasma arterial prostaglandin (PG) E2 was significantly increased in borderline hypertensive patients (BH) (28.5 +/- 6.7 pg/ml) in comparison with sustained essential hypertensive patients (EH) (11.6 +/- 3.2 pg/ml) and in comparison with control normotensive subjects (NTS) (5.8 +/- 1.4 pg/ml). 2. Plasma arterial PGE2 was positively significantly correlated with cardiac index and negatively significantly correlated with total peripheral resistance in basal conditions. 3. Indomethacin induced more pronounced haemodynamic changes in borderline than in sustained hypertensive patients, with a significant increase in arterial blood pressure and total peripheral resistance and a significant decrease in stroke volume and cardiac index. 4. Indomethacin significantly decreased arterial PGE2 in borderline hypertensive patients. The decrease was less important in sustained hypertensive patients. 5. In the overall population, a significant positive correlation between arterial PGE2 concentration and cardiac index was observed before and after indomethacin treatment. 6. The study suggests an important role of PGE2 in the regulation of cardiac output (positive inotropic effect) and blood pressure of essential hypertensive patients.
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PMID:Central haemodynamics and plasma prostaglandin E2 in borderline and sustained essential hypertensive patients before and after indomethacin. 694 67

The effect of indomethacin (3mg/kg IA) preloading on the pathophysiology of a model of acute cerebral ischaemia has been tested. Primates anaesthetised with alpha-chloralose were used. Indomethacin reduced basal blood flow by 39% and reduced CO2 reactivity by 71%. Water content changes of the cerebral cortex and relationships between blood flow and extracellular potassium (Ke), and calcium (Cae) activities have been measured. Indomethacin infusion did not effect the water content of the left side but there was more water in all regions of the right hemisphere which were rendered ischaemic. There water increases were significant for blood flows greater than 5ml/100g/min in exposed areas. There was a significant increase in the flow thresholds for change in Ke and Cae. Possible mechanisms for these changes have been discussed.
Stroke
PMID:Modulation of the pathophysiology of primate focal cerebral ischaemia by indomethacin. 706 74

The concentrations of the arachidonic acid metabolites, PGD2, PGF2 alpha and 6-keto-PGF1 alpha, were measured in the cerebral hemispheres of gerbils subjected to unilateral carotid occlusion. Approximately 37 percent of the animals with occlusion had symptoms of cerebral ischemia. In those animals PGD2 and PGF2 alpha levels were elevated in both hemispheres. The levels of 6-keto-PGF1 alpha increased only slightly. There was no change of prostaglandin levels in asymptomatic animals. Indomethacin inhibited the increase in the levels of these arachidonic acid metabolites but did not alter brain swelling as judged by a decrease in specific gravity after 6 hours occlusion.
Stroke
PMID:Effect of unilateral common carotid artery occlusion on levels of prostaglandins D2, F2 alpha and 6-keto-prostaglandin F1 alpha in gerbil brain. 721 72

We investigated mechanisms by which hypoxia produces relaxation of the aorta and tested the hypothesis that these mechanisms are altered during chronic hypertension. Tension of thoracic aortae from normotensive Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) was measured in an organ bath under control conditions and at two levels of hypoxia. In WKY rats, mild and severe hypoxia produced relaxation of the aortae (precontracted with phenylephrine) by 33 +/- 4% and 82 +/- 3%, respectively (mean +/- SEM). Removal of endothelium or administration of NG-nitro-L-arginine (10(-4) mol/L), an inhibitor of nitric oxide synthase, abolished relaxation of the aortae in response to mild hypoxia but did not affect relaxation during severe hypoxia. Glibenclamide (10(-6) mol/L), an inhibitor of potassium channels, attenuated relaxation of the aortae during mild and severe hypoxia by 49 +/- 16% and 74 +/- 4%, respectively. In SHRSP, mild hypoxia produced little relaxation of the aortae (3 +/- 4%, P < .05 compared with WKY). Indomethacin did not increase relaxation to mild hypoxia in SHRSP, which suggests that a cyclooxygenase-derived contracting factor does not contribute to impaired relaxation. Severe hypoxia relaxed the aortae by 86 +/- 4% in SHRSP, and glibenclamide inhibited this response by 60 +/- 9%. These findings suggest that relaxation of the aorta in response to mild hypoxia in WKY rats is mediated primarily by endothelium-derived relaxing factor, and the response to mild hypoxia is markedly impaired in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relaxation of the aorta during hypoxia is impaired in chronically hypertensive rats. 753 13

1. Endothelium-dependent relaxation (EDR) in aortic rings from young (8 weeks) and adult (16 weeks and 20 weeks) stroke-prone spontaneously hypertensive rats (SHRSP) was investigated in comparison with age-matched Wistar-Kyoto rats (WKY). 2. At 8 weeks, acetylcholine (3 x 10(-9)-10(-5) mol/L) and ionomycin (4 x 10(-8)-10(-6) mol/L)-induced EDR in SHRSP aortae was significantly enhanced compared to that in WKY aortae. Mechanical denudation of the endothelium completely abolished, and pretreatment of aortae with NG-monomethyl L-arginine (1 mmol/L), an inhibitor of nitric oxide formation, greatly reduced the relaxation in both strains. Indomethacin (10(-5) mol/L), a cyclo-oxygenase inhibitor that blocks the production of endothelium-derived contracting factors, did not significantly alter the relaxation by acetylcholine at this age. There was no difference in endothelium-independent relaxation of denuded aortae by sodium nitroprusside (10(-9)-10(-6) mol/L) and 8-bromoguanosine 3', 5'-cyclic monophosphate (10(-6)-10(-3) mol/L). 3. In adult SHRSP with established hypertension, however, the acetylcholine (10(-8)-10(-5) mol/L)-induced relaxation markedly diminished at any of the concentrations tested compared to that observed in 8 weeks old SHRSP and WKY at 8-20 weeks of age. This finding differed from other observations where the relaxation in SHRSP was impaired only at higher concentrations of acetylcholine. Indomethacin pretreatment of aortae from 20 week old SHRSP restored acetylcholine-induced EDR to a level comparable with that in age-matched WKY.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhancement of endothelium-dependent relaxation in the aorta from stroke-prone spontaneously hypertensive rats at developmental stages of hypertension. 788 76

Vascular smooth muscle from stroke-prone spontaneously hypertensive rats has an increased responsiveness to the vasoconstrictors angiotensin II and serotonin. This abnormality is postulated to contribute to the hypertension characteristic of this strain of rats. We hypothesized that a portion of the increased responsiveness may be due to altered function of G proteins. This hypothesis was tested using mastoparan, a peptide that mimics ligand-bound receptors to stimulate G proteins directly. In addition, we investigated the mechanism of mastoparan-induced contraction of vascular smooth muscle. Changes in isometric tension were recorded in denuded carotid artery strips from hypertensive and normotensive (Wistar-Kyoto) rats. Vascular strips from the hypertensive rats had a significantly greater response to mastoparan at all concentrations between 10(-8) and 10(-5) mol/L. A G protein inhibitor, N-ethylmaleimide (10(-3) mol/L), attenuated the response to mastoparan (10(-7) mol/L) (67 +/- 4% of control response), whereas pertussis toxin treatment did not. Inhibition of phospholipase C also significantly decreased the mastoparan-induced response (23 +/- 12% of control), and nifedipine (10(-3) mol/L), a calcium channel blocker, completely blocked the mastoparan-induced contraction. Indomethacin treatment did not affect the mastoparan contraction even though mastoparan has been shown to stimulate phospholipase A2 in other cell types. In conclusion, we observed an increased response in carotid arteries from genetically hypertensive rats to a pharmacological intervention that appears to act via G protein-linked phospholipase C stimulation and L-type calcium channel activation, suggesting that the increased vascular reactivity in stroke-prone spontaneously hypertensive rats is due in part to altered function of G proteins.
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PMID:Enhanced vascular reactivity to mastoparan, a G protein activator, in genetically hypertensive rats. 820 33

1. The influence of the passive force on the contraction and endothelium-dependent relaxation in aortae of normotensive Wistar Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) were compared. 2. Force changes of endothelium-intact and -removed preparations were measured isometrically by a force-displacement transducer. Endothelium-dependent relaxation was observed by applying acetylcholine to the preparation precontracted in the presence of 5 x 10(-7) mol/L noradrenaline. 3. The preparations showed spontaneously developed tension (tone) that increased with the increase in the passive force. The effect of passive force was greater in preparations from SHRSP. Contraction initiated by noradrenaline was also increased by passive force up to 30 mN, then showed a tendency to decrease. 4. Endothelium-dependent relaxation was depressed as the passive force was increased. Preparations from SHRSP showed impaired endothelium-dependent relaxation and were influenced by passive force to a lesser degree when compared with preparations from WKY rats. 5. Relaxation by sodium nitroprusside was influenced by passive force to a much lesser extent than that by acetylcholine. 6. Indomethacin potentiated endothelium-dependent relaxation and blocked the effect of passive force in both preparations. 7. The difference in relaxation and the effect of passive force is primarily caused by the difference in the release of endothelium-derived contracting factor, which is thought to be a product of the cyclo-oxygenase pathway of the arachidonic acid cascade.
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PMID:Spontaneous and agonist-induced contractions and endothelium-dependent relaxation in aortae from SHRSP and WKY rats under various levels of passive force. 880 May 70


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