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

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

The important role played by nitric oxide (NO) in the central nervous system has largely been emphasized in the recent literature. It can originate at least from four different sources: the endothelium of cerebral vessels, the immunostimulated microglia and astrocytes, the nonadrenergic noncholinergic nerve, and the glutamate neuron. NO has been implicated in a large number of pathologies (such as neurotoxicity in Alzheimer's disease and Huntington's disease, cerebral ischemia, stroke, and anxiety) and also in normal physiological functions (such as memory and learning, regulation of the cerebrovascular system, modulation of the wakefulness, mediation of nociception, olfaction, food intake and drinking, regulation of noradrenaline, and dopamine release). The aim of this paper is to review and to integrate the most recent advances in our understanding of the roles of NO in the brain.
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PMID:Nitric oxide: a new messenger in the brain. 790 24

Endothelial dysfunction appears to be an early event in most forms of cardiovascular disease. The dysfunction may involve a decreased formation, inactivation, or action of nitric oxide or prostacyclin as well as an increased formation of contracting factors, eg, prostaglandin H2 and endothelin-1. Cardiovascular drugs can improve endothelial function either indirectly through their effects on cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes or directly through endothelial actions. Direct and indirect endothelial protective effects of cardiovascular drugs may significantly contribute to normal organ perfusion and a reduced incidence of myocardial infarction, stroke, and renal failure in patients. Endothelium-dependent vascular regulation in health and in various cardiovascular diseases as well as the effects of currently available cardiovascular drugs are reviewed.
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PMID:Possibilities and perspectives of pharmacotherapy for endothelial protection. 792 59

The role of blood platelets in the pathogenesis of atherosclerosis, thrombosis, thromboembolism and stroke (hemorrhagic/thrombotic) is well established. In view of this recognized role played by platelets in the complications associated with coronary artery disease and cerebrovascular disease, there is considerable interest in the pharmacology of platelet activation inhibitory drugs. These drugs exert their effect by blocking several different activation signalling mechanisms. Some of the known compounds that modulate platelet function include: inhibitors of arachidonic acid metabolism (nonsteroidal anti-inflammatory drugs and thromboxane synthetase inhibitors), drugs that alter membrane phospholipid composition (omega 3 fatty acids), stimulators of adenylyl cyclase and guanylyl cyclase (PGE1, PGI2, PGD2/ERRF [nitric oxide], nitroglycerin, nitroprusside), phosphodiesterase inhibitors (dipyridamole and methylxanthines) and calcium antagonists (verapamil, nifedipine, diltiazem). Current research on the pharmacology of platelet activation inhibitory drugs is focused on the development of specific receptor antagonists (antibodies, peptides, receptor antagonists). Since platelets have multiple mechanisms for achieving activation, and the process of thrombosis involves multicellular modulation of platelet activity, it will be rather difficult to develop a compound that is capable of causing complete inhibition of activation mechanisms. Therefore, future research will be devoted to development of designer drugs that will be used for preventing discrete platelet responses. This approach may be useful as total inhibition of platelet activation, although it may prevent thrombotic events, may possibly precipitate hemorrhagic conditions. A better understanding of cell signalling pathways and the mechanisms involved in the pathogenesis of cardiovascular cerebrovascular disease will facilitate the development of efficient antiplatelet drugs.
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PMID:Pharmacology of platelet activation-inhibitory drugs. 806 66

We studied whether administration of nitric oxide (NO) donors reduces the ischemic damage resulting from middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats (SHRs). In halothane-anesthetized and ventilated SHRs, the MCA was occluded. CBF was monitored using a laser-Doppler flowmeter. Three to five minutes after MCA occlusion, the NO donors sodium nitroprusside (SNP; 3 mg/kg/h) or 3-morpholino-sydnonimine (SIN 1; 1.5-6 mg/kg/h) were administered into the carotid artery for 60 min. As a control, the effect of papaverine (3.6 mg/kg/h), a vasodilator that acts independently of NO, was also studied. The hypotension evoked by these agents was counteracted by intravenous infusion of phenylephrine. At the end of the infusion, rats were allowed to recover. Stroke size was determined 24 h later in thionin-stained sections. In sham occluded rats, SNP (n = 5), SIN 1 (n = 5), and papaverine (n = 5) produced comparable increases in CBF (p > 0.05 from vehicle). After MCA occlusion, SNP (n = 5) and SIN 1 (n = 5), but not papaverine (n = 5), enhanced the recovery of CBF (p < 0.05 from vehicle) and reduced the size of the infarct by 28 +/- 12 and 32 +/- 7%, respectively (mean +/- SD; p < 0.05 from vehicle). To determine whether NO donors could act by inhibiting platelet aggregation, we studied the effect of SNP on collagen-induced platelet aggregation. Intracarotid administration of SNP (3 mg/kg/h for 60 min) did not affect platelet aggregation to collagen, suggesting that the protective effect of NO donors was not due to inhibition of platelet function. We conclude that NO donors increase CBF to the ischemic territory and reduce the tissue damage resulting from focal ischemia. The protective effect may result from an increase in CBF to the ischemic territory, probably the ischemic penumbra. These findings suggest that NO donors may represent a new therapeutic strategy for the management of acute stroke.
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PMID:Nitric oxide donors increase blood flow and reduce brain damage in focal ischemia: evidence that nitric oxide is beneficial in the early stages of cerebral ischemia. 811 18

Nitric oxide (NO), previously identified with endothelium derived relaxing factor (EDRF), is thought to play a role in central neurotransmission: it is characterized by high lipid solubility and short half life, and NO-synthase, the enzyme which generates NO from L-arginine, has been found in the central nervous system (CNS), both in neuronal and glial cells. NO is believed to be involved in many neural events, such as neurotoxicity from N-methyl-D-aspartate (NMDA) receptor overstimulation, brain damage from vascular stroke, fever, nociception, memory and appetite control. Recent evidence implicates NO as a modulator of endocrine secretions, with inhibition of insulin, growth hormone (GH) and oxytocin release and stimulation of vasopressin (AVP), adrenocorticotropin (ACTH) and corticotropin releasing hormone (CRH) release. NO and prostaglandins could mediate neuroendocrine activities of cytokines such as interleukin-1 (IL-1) and interleukin-2 (IL-2), particularly in the CNS.
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PMID:Nitric oxide: a gas as a modulator of neuroendocrine secretions. 818 Dec 9

Cardiovascular risk is higher in men than in women, and also more prevalent in postmenopausal than in premenopausal women, especially if not treated by estrogens. These differences may be due, in part, to a cardioprotective action of sex hormones, mainly estrogens. However, only a limited part of this protection may be attributed to metabolic modifications induced by replacement therapy with estrogen. Therefore, it remains to be determined which other cardioprotective mechanisms influenced by sex steroids might be involved. It has been demonstrated that the menopause is associated with an increase in uterine arterial pulsatility index, reflecting increased peripheral resistance, while the administration of estrogens has an opposite effect at this level. In Doppler studies, estrogen replacement therapy was also associated with an increase in stroke volume and flow acceleration in the aorta. This suggests a positive inotropic effect of estrogens. Using technetium scanning, it was found that women at an early phase of menopause have a stronger myocardial contractility than women of a similar age whose menopause is of longer duration. These effects of estrogens on hemodynamic characteristics might be controlled by vasoregulatory hormones such as endothelin(s) or endothelial-derived relaxing factor (EDRF), now identified as nitric oxide (NO). Indeed, sex-associated differences in endothelin have been observed. Such are some of the mechanisms by which estrogen administration might effect a cardiovascular protection. At the present time, however, conclusive data are not available.
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PMID:Cardiovascular protection by estrogen: a hemodynamic mechanism? 819 39

Deendothelialized rings of rabbit aorta relax after exposure to UV light because of release of a relaxing factor that is similar if not identical to nitric oxide. We tested the hypothesis that production of the photo-induced relaxing factor is impaired in a rat model of genetic hypertension. Thoracic aortas were removed from adult Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. The vessels were cut into rings, denuded of endothelium, and placed in a muscle bath for isometric force measurement. Rings were contracted with phenylephrine, and relaxation was measured after exposure to UV light. Aortic rings from stroke-prone spontaneously hypertensive rats relaxed to a greater extent after exposure to UV light than did rings from Wistar-Kyoto rats. An inhibitor of nitric oxide synthase (N omega-nitro-L-arginine) greatly potentiated the relaxation responses to light in both strains, and these enhanced relaxations were attenuated by tetraethylammonium chloride, potassium chloride, ouabain, or inhibitors of guanylate cyclase. These results suggest that UV irradiation induces relaxation in aortic smooth muscle that is greater in hypertensive than normotensive rats and is greatly enhanced after addition of inhibitors of nitric oxide production. Thus, the unidentified photo-induced relaxing factor is not solely nitric oxide but may also represent either a hyperpolarizing factor, because depolarization blocks the responses entirely, or possibly smooth muscle guanylate cyclase that might itself be photoactivable.
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PMID:A photoactivable source of relaxing factor in genetic hypertension. 820 24

1. A series of experiments was carried out on 3 separate groups of male Long Evans rats, chronically instrumented for the measurement of regional haemodynamics, to compare the effects of NG,NG, dimethyl-L-arginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA), and their reversibility by the nitric oxide donors, S-nitroso-N-acetyl-penicillamine (SNAP), S-nitroso-glutathione (SNOG), sodium nitroprusside (SNP), and the vasodilator, hydralazine. 2. As previously reported for L-NMMA, ADMA (1-100 mg kg-1) caused dose-dependent pressor and bradycardic effects, accompanied by renal, mesenteric and hindquarters vasoconstrictions. The magnitude and duration of these effects were similar for ADMA and L-NMMA, consistent with their being equipotent inhibitors of nitric oxide synthase. 3. Infusion of SNAP or SNOG (300 micrograms kg-1 h-1) after injection of ADMA or L-NMMA (100 mg kg-1) reversed the pressor but did not abolish the vasoconstrictor, effects of ADMA or L-NMMA. However, a higher dose of SNAP (3 mg kg-1 h-1) caused complete reversal of the pressor and mesenteric haemodynamic effects of ADMA (100 mg kg-1), although its renal and hindquarters vasoconstrictor effects were not abolished. 4. Infusion of SNP (300 micrograms kg-1 h-1) after administration of L-NMMA (100 mg kg-1), caused complete reversal of its pressor and mesenteric and hindquarters haemodynamic effects, and reduced substantially its renal vasoconstrictor action; hydralazine (7.5 mg kg-1 h-1) was almost as effective as SNP in reversing all these variables. 5. In animals chronically instrumented for the measurement of cardiac haemodynamics, ADMA(100 mg kg-1) caused a pressor effect accompanied by a rise in central venous pressure, and reductions in heart rate, cardiac index, stroke index, peak aortic flow, maximum rate of rise of aortic flow and total peripheral conductance. The reversal of the pressor effect of ADMA by SNAP (300 microg kg-1 h-1) was accompanied by a reduction of central venous pressure below resting levels and a further diminution of stroke index; all other variables showed an increase, but they still remained below resting levels (with the exception of heart rate).6. Thus, following inhibition of NO synthesis, pharmacological intervention with NO donors, or other vasodilators, may cause normalisation of the mean arterial pressure without necessarily returning all associated cardiovascular variables to normal.
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PMID:Regional and cardiac haemodynamic effects of NG, NG,dimethyl-L-arginine and their reversibility by vasodilators in conscious rats. 830 87

The influence of dietary sodium restriction and angiotensin II blockade on hypertension induced by a 25-day period of administration of the inhibitor of nitric oxide synthesis NG-nitro-L-arginine-methyl ester (10 mg/kg twice daily by gavage) was assessed in Wistar rats fed a normal or low sodium diet. In addition, the angiotensin II receptor blocker losartan (30 mg/kg once daily by gavage) was administered before and during NG-nitro-L-arginine-methyl ester in rats fed the normal sodium diet. At the end of the studies, conscious systolic arterial pressure increased similarly in NG-nitro-L-arginine-methyl ester-treated groups maintained on normal or low sodium intake. Moreover, a 25% reduction in cardiac output due to a decrease in stroke volume was observed in both groups. A slight but significant cardiac hypertrophic response was observed in hypertensive rats irrespective of sodium intake. At the completion of studies, plasma renin activity was similar to corresponding controls in the hypertensive groups on normal or low sodium intake. Losartan totally prevented the development of hypertension as well as the decrease in stroke volume and cardiac hypertrophy associated with NG-nitro-L-arginine-methyl ester treatment in rats on normal sodium intake. In conclusion, hypertension resulting from long-term blockade of nitric oxide synthesis was not affected by dietary sodium restriction. A crucial role for the renin-angiotensin system was demonstrated in this new model of hypertension.
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PMID:Sodium and angiotensin in hypertension induced by long-term nitric oxide blockade. 850 4


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