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

To study potential central adrenoceptor alterations in the hypertension, we have determined alpha 1, alpha 2 and beta-adrenoceptors using [3H]WB4101, [3H]yohimbine and [3H]DHA in the brain regions of spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and renal hypertensive rats. There was a significant increase in specific [3H]WB4101 binding only in the hypothalamus of SHR and SHRSP at 16-24 weeks of age compared to that of age-matched Wistar-Kyoto rats (WKY). Scatchard analysis revealed a 28-33% increase in the Bmax value for hypothalamic [3H]WB4101 binding without a change in the Kd value, suggesting a change in the receptor density. An increased density of alpha 1-adrenoceptors was consistently observed in the prehypertensive (5 weeks) and developmental (10 weeks) stages of spontaneous hypertension. In contrast, there was no alpha 1-adrenoceptor alteration in the hypothalamus of rats with renal hypertension. The receptor alteration in the SHRSP hypothalamus was not abolished by a chronic hypotensive treatment which prevented the development of hypertension, thereby suggesting that an increased density of the alpha 1-adrenoceptors in spontaneous hypertension does not occur secondarily to the elevation of blood pressure. The SHRSP hypothalamus showed significantly lowered levels of noradrenaline. There was no change in specific binding of [3H]yohimbine and [3H]DHA in the brain regions of SHRSP, except the brainstem which showed a significant decrease in the [3H]yohimbine binding. Thus, the present study suggests an important role for hypothalamic alpha 1-adrenoceptors in the pathogenesis of spontaneous hypertension.
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PMID:Specific increase of hypothalamic alpha 1-adrenoceptors in spontaneously hypertensive rats: effect of hypotensive drug treatment. 299 33

Pressure overload left ventricular (LV) hypertrophy was produced by banding the ascending aorta of puppies and allowing them to grow to adulthood. LV free wall weight per body weight increased by 87% from a normal value of 3.23 +/- 0.19 g/kg. Hemodynamic studies of conscious dogs with LV hypertrophy and of normal, conscious dogs without LV hypertrophy showed similar base-line values for mean arterial pressure, heart rate, and LV end-diastolic pressure and diameter. LV systolic pressure was significantly greater, P less than 0.01, and LV stroke shortening was significantly lss, P less than 0.01, in the LV hypertrophy group. In both normal and LV hypertrophy groups, increasing bolus doses of norepinephrine or isoproterenol produced equivalent changes in LV dP/dt. beta-adrenergic receptor binding studies with [3H]-dihydroalprenolol ( [3H]DHA) indicated that the density of binding sites was significantly elevated, P less than 0.01, in the hypertrophied LV plasma membranes (111 +/- 8.8, n = 8), as compared with normal LV (61 +/- 5.6 fmol/mg protein, n = 11). The receptor affinity decreased, i.e., disassociation constant (KD) increased, selectively in the LV of the hypertrophy group; the KD in the normal LV was 6.8 +/- 0.7 nM compared with 10.7 +/- 1.8 nM in the hypertrophied LV. These effects were observed only in the LV of the LV hypertrophy group and not in the right ventricles from the same dogs. The plasma membrane marker, 5' -nucleotidase activity, was slightly lower per milligram protein in the LV hypertrophy group, indicating that the differences in beta-adrenergic receptor binding and affinity were not due to an increase in plasma membrane protein in the LV hypertrophy group. The EC50 for isoproterenol-stimulated adenylate cyclase activity was similar in both the right and left ventricles and in the two groups. However, maximal-stimulated adenylate cyclase was lower in the hypertrophied left ventricle. Plasma catecholamines were similar in the normal and hypertrophied groups, but myocardial norepinephrine was depressed in the dogs with LV hypertrophy (163 +/- 48 pg/mg) compared with normal dogs (835 +/- 166 pg/mg). Thus, severe, but compensated LV hypertrophy, induced by aortic banding in puppies, is characterized by essentially normal hemodynamics in adult dogs studied at rest and in response to catecholamines in the conscious state. At the cellular level, reduced affinity and increased beta-adrenergic receptor number characterized the LV hypertrophy group, while the EC50 for isoproterenol-stimulated adenylate cyclase activity was normal. By these mechanisms, adequate responsiveness to catecholamines is retained in conscious dogs with severe LV hypertrophy.
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PMID:Effects of pressure overload, left ventricular hypertrophy on beta-adrenergic receptors, and responsiveness to catecholamines. 632 5

The effect of dietary fish oils on development of hypertension and vascular response in vitro were studied in rats and a primate. Dietary fish oils (MaxEPA and an n-3 ethyl ester concentrate of higher EPA and DHA content) were administered to spontaneously hypertensive (SHR), stroke-prone spontaneously hypertensive (SHR-SP) and a backcross of SHR and Wistar Kyoto (SHR/WKY) rats from 4-16 weeks of age. Blood pressure was monitored during the feeding period and vascular responses measured in the aorta and mesenteric vascular bed in vitro. Depending on the strain of rat used and the composition of the fish oil the attenuation in blood pressure was 10-26 mmHg. Fish oils attenuated the response mediated by sympathetic nerve stimulation or intralumenal norepinephrine in the perfused mesenteric vascular bed preparation from the SHR. This attenuation was more pronounced for fish oils enriched with eicosapentaenoic acid and docosahexaenoic acid and was more prominent in the SHR and SHR/WKY backcross than it was in the SHR-SP. Prostanoid synthesis or nitric oxide modulation of alpha-adrenoceptor responses were shown not to be involved in the attenuation of vascular responses produced by fish oil. The maximum contraction of aortic ring preparations in response to norepinephrine (NE) was significantly smaller in SHR than WKY rats fed olive oil and for SHR rats maintained on fish oils the contraction was close to WKY olive oil values. Evidence was obtained also for a modulation of vasoconstrictor responses by dietary fish oils in the perfused mesenteric bed of the marmoset monkey.
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PMID:Fish oils modulate blood pressure and vascular contractility in the rat and vascular contractility in the primate. 767 Jun 52

Dietary fish oils rich in n-3 polyunsaturated fatty acids can modulate a diverse range of factors contributing to cardiovascular disease. This study examined the relative roles of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA) which are the principal n-3 polyunsaturated fatty acids regarded as candidates for cardioprotective actions. At low dietary intakes (0.4-1.1% of energy (%en)), docosahexaenoic acid but not eicosapentaenoic acid inhibited ischaemia-induced cardiac arrhythmias. At intakes of 3.9-10.0%en, docosahexaenoic acid was more effective than eicosapentaenoic acid at retarding hypertension development in spontaneously hypertensive rats (SHR) and inhibiting thromboxane-like vasoconstrictor responses in aortas from SHR. In stroke-prone SHR with established hypertension, docosahexaenoic acid (3.9-10.0%en) retarded the development of salt-loading induced proteinuria but eicosapentaenoic acid alone was ineffective. The results demonstrate that purified n-3 polyunsaturated fatty acids mimic the cardiovascular actions of fish oils and imply that docosahexaenoic acid may be the principal active component conferring cardiovascular protection.
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PMID:The cardiovascular protective role of docosahexaenoic acid. 874 Nov 70

1. We previously reported that hypertension in stroke-prone spontaneously hypertensive rats (SHRSP) caused renal membrane phospholipid degradation. Renal phospholipase A2 activity increased and membranous phospholipids decreased along with age in SHRSP. Membranous abnormalities induced by membrane fluidity and calcium permeability changes may contribute to the elevation of blood pressure in SHRSP. DHA, a major component of fish oil, constitutes a part of membrane phospholipid acylchains. 2. The purpose of this study was to clarify the effect of DHA on the relationship between the renal function and the development of hypertension in SHRSP. 3. Six week old male SHRSP were fed a semi-purified diet supplemented with DHA (0, 1 and 5%) for 14 weeks. 4. The systolic blood pressure of control SHRSP (DHA 0%) significantly increased from 120.2 mmHg to 202.9 mmHg. This increase in systolic blood pressure was significantly inhibited in a dose-dependent manner by 1 and 5% DHA diet to 167.8 to 149.8 mmHg, respectively. 5. Serum creatinine concentration and blood urea nitrogen (BUN) were significantly lower in DHA (5%)-treated SHRSP than in the control SHRSP. 6. These results indicate that DHA prevents the development of hypertension in SHRSP, which is associated with changes in renal function.
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PMID:Dietary docosahexaenoic acid (22: 6n-3) prevents the development of hypertension in SHRSP. 907 5

The effects of DHA treatment on intracellular Ca2+ dynamics in aortic smooth muscle cells isolated from young stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar Kyoto rats (WKY) were investigated. The resting intracellular Ca2+ concentration ([Ca2+]i) before stimulation and the peak [Ca2+]i induced by 5-HT, angiotensin II and depolarizing concentration of KC1 were higher in SHRSP than in WKY. When added to the culture medium for 2 days, DHA at a concentration of 30 microM significantly suppressed the peak [Ca2+]i induced by these stimulants in aortic smooth muscle cells isolated from WKY, whereas smooth muscle cells of SHRSP were refractory to the suppression. DHA had no suppressive effect on the 5-HT-induced increase in the inositol triphosphate production. The present study indicates that DHA can suppress receptor-mediated Ca2+ influx, at least, through the voltage-dependent channel, in vascular smooth muscle cells. Since the intracellular Ca2+ plays an important role in regulating vascular tone, the suppressive effect of DHA on [Ca2+]i in vascular smooth muscle cells may be contributed to the beneficial properties of DHA on cardiovascular disorders. The precise mechanisms of action remain to be elucidated.
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PMID:Effect of docosahexaenoic acid on intracellular calcium dynamics in vascular smooth muscle cells from normotensive and genetically hypertensive rats. 992 Mar 44

Aberrations in neural signaling, converging to and diverging from oxidative metabolism and blood supply, contribute to the initiation and maintenance of inflammatory responses, neuronal degeneration, and age-related cognitive decline in Alzheimer's disease (AD). Hypoxia/ischemia triggers phospholipase A2, leading to the accumulation of free arachidonic and docosahexaenoic acids (AA, DHA), as well as that of lysophospholipids. Some of these bioactive lipid messengers in turn give rise to several downstream lipid messengers, such as platelet-activating factor (PAF) and ecosanoids (prostaglandins and leukotrienes). Eicosanoid synthesis is highly regulated in hypoxia and in reperfusion subsequent to ischemia. As one of the consequences, mitochondrial function is disrupted and reactive oxygen species (ROS) both contribute to the expansion of cellular inflammatory responses and reduce the expression of genes required to maintain synaptic structure and function. On the other hand, pro-inflammatory genes are up-regulated. One of these, the inducible cyclooxygenase-2 (COX-2), along with oxygen-starved mitochondria, comprise the major sources of ROS in the brain during hypoxia, ischemia, and reperfusion. One outcome is a sustained metabolic stress that drives progressive dysfunction, apoptosis and/or necrosis, and brain cell death. How hypoxia modulates oxygen-sensitive gene expression is not well understood. Pro-inflammatory gene families that contribute to neurodegeneration are transiently activated in part by the heterodimeric oxygen-sensitive DNA-binding proteins nuclear factor for kappa B (NF-kappaB) and hypoxia-inducible factor-alpha (HIF-1alpha). Here the authors summarize current studies supporting the hypothesis that synaptically-derived lipid messengers play significant roles in ischemic stroke and that hypoxia is an important contributor to the onset and progression of AD neurodegeneration.
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PMID:Hypoxia signaling to genes: significance in Alzheimer's disease. 1242 61

(1) The WHI study was published in 2002: a randomised double-blind placebo-controlled clinical trial in more than 16 000 women with an average age of 63 years at enrollment. The paper reports data on the long-term adverse effects of combined equine estrogen-progestin hormone replacement therapy, taken for 5 years. (2) On average, a yearly excess of 19 severe adverse events per 10 000 women occurred in the estrogen-progestin group. Relative to the placebo group, there were an extra 8 pulmonary embolisms, 7 coronary events, 8 strokes and 8 cases of invasive breast cancer. In contrast, there were 6 fewer colorectal cancers and 5 fewer hip fractures in the active treatment group. (3) The differences in the frequency of coronary events and venous thromboembolism emerged after the first year of treatment, while the curves for stroke and breast cancer diverged after the second and fifth years, respectively. (4) The overall mortality rate did not differ between the two groups. (5) A placebo-controlled trial of the same hormone combination (HERS trial), given for 4.1 years as secondary prophylaxis against coronary heart disease was published in 1998. The drug was ineffective during the trial, and during unblinded post-trial follow-up of 2 321 women for an average of 2.7 years (HERS II study). (6) The estrogen-progestin combination used in these trials did not reduce the risk of coronary heart disease (in primary or secondary prophylaxis) or the risk of stroke. On the contrary, both risks increased. (7) The increased incidence of deep venous thrombosis and/or pulmonary embolism associated with estrogen-progestin replacement therapy was confirmed in these trials, even among women with no relevant history. (8) The WHI trial also confirmed the increased risk of breast cancer in women on hormone replacement therapy, but did not study its impact on outcome or mortality. (9) The WHI trial confirmed the beneficial impact of estrogen-progestin combination therapy on the risk of osteoporotic fracture. An average of 5 hip fractures were avoided each year per 10 000 women treated (10 versus 15 observed cases per 10 000 women per year), together with 6 symptomatic vertebral fractures (9 versus 15 cases) and 44 osteoporotic fractures (147 versus 191 cases). It is not known whether the benefit observed at the end of the trial persisted after the end of treatment. (10) In practice, the decision to prescribe hormone replacement therapy, and the optimal duration of treatment, must be weighed up according to each individual's risk factors. And the decision to treat or not to treat must be regularly re-assessed. Women must be informed of the potential risks and benefits, and must be monitored. They should also be advised not to use less well assessed treatments such as phytoestrogens, DHEA and tibolone. (11) Health authorities, especially in Europe, must organise comparative trials to assess the benefits and risks of other hormone combinations used by perimenopausal and postmenopausal women.
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PMID:Postmenopausal hormone therapy: cardiovascular risks. 1267 30

Diabetics have at least twice the risk of stroke and may show performance deficit in a wide range of cognitive domains. The mechanisms underlying this gradually developing end-organ damage may involve both vascular changes and direct damage to neuronal cells as a result of overproduction of superoxide by the respiratory chain and consequent oxidative stress. The study aimed to assess the role of oxidative stress on the aldose reductase-polyol pathway, on advanced glycated end-product (AGE)/AGE-receptor interaction, and on downstream signaling in the hippocampus of streptozotocin-treated rats. Data show that, in diabetic rats, levels of prooxidant compounds increase, whereas levels of antioxidant compounds fall. Receptor for AGE and galectin-3 content and polyol flux increase, whereas glyceraldehyde-3-phosphate dehydrogenase activity is impaired. Moreover, nuclear factor kappaB (p65) transcription factor levels and S-100 protein are increased in the hippocampus cytosol, suggesting that oxidative stress triggers the cascade of events that finally leads to neuronal damage. Dehydroepiandrosterone, the most abundant hormonal steroid in the blood, has been reported to possess antioxidant properties. When dehydroepiandrosterone was administered to diabetic rats, the improved oxidative imbalance and the marked reduction of AGE receptors paralleled the reduced activation of nuclear factor kappaB and the reduction of S-100 levels, reinforcing the suggestion that oxidative stress plays a role in diabetes-related neuronal damage.
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PMID:Up-regulation of advanced glycated products receptors in the brain of diabetic rats is prevented by antioxidant treatment. 1616 20

Results of previous studies on fish intake and stroke risk have been inconclusive. Different stroke types have often not been separated. Our aim was to elucidate whether intake of fish, Hg or the sum of proportions of fatty acids EPA (20 : 5n-3) and DHA (22 : 6n-3) influence the risk of haemorrhagic or ischaemic stroke. Within a population-based cohort from a community intervention programme, 369 stroke cases and 738 matched controls were identified and included in the present nested case-control study. Information on fish intake had been recorded at recruitment, i.e. before diagnosis. Hg levels were determined in erythrocyte membranes, also collected at recruitment, and the relative content of fatty acids was measured in erythrocyte membranes or plasma phospholipids. The results showed that in women there was a non-significant decrease in stroke risk with increasing fish intake (OR 0.90 (95 % CI 0.73, 1.11) per meal per week). The risk in women differed significantly (P = 0.03) from that in men, in whom the OR for stroke rose with increasing fish intake (OR 1.24 (95 % CI 1.01, 1.51) per meal per week). The corresponding risk in men for Hg was 0.99 (95 % CI 0.93, 1.06), and for the sum of proportions of EPA and DHA 1.08 (95 % CI 0.92, 1.28). We conclude that the relationship between stroke risk and fish intake seems to be different in men and women. Increased levels of EPA and DHA do not decrease the risk for stroke and there is no association between stroke risk and Hg at these low levels.
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PMID:Fish intake, mercury, long-chain n-3 polyunsaturated fatty acids and risk of stroke in northern Sweden. 1753 90


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