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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of intrauterine hypoxia-ischemia (HI) on brain functional development in the term rat were examined in cerebellar granule cell cultures obtained from an in utero HI model. On gestation d 17, HI conditions were achieved by complete clamping of the uterine vasculature for designated durations followed by removal of the clamps to permit reperfusion. Sham operation (surgery without vasculature clamping) was performed as the control. After surgery, the uterine horns were returned to dam's abdomen to let the pups deliver naturally. Severe HI insult from the surgical manipulation was evident in that the lactate levels of fetal brain increased, and fetal blood pH decreased with the duration of vasculature clamping up to 1 h. The experimental HI insult up to 1 h did not affect fetal survival rate, but retarded growth of fetuses or newborns was observed in the 1 h HI group. N-Methyl-D-aspartate (NMDA)- and kainate (KA)-stimulated cGMP formation and glutamate accumulation were measured in cerebellar granule cell cultures from 8-d-old pups suffering from various durations of antenatal HI insult. NMDA (100 microM)-induced elevation of cGMP was further augmented by a 10-35-min HI insult as compared with the control cells (62.4-78.2 versus 49 pmol/mg protein). In the presence of L-NG-monomethyl-arginine (L-NMMA, 150 microM), a nitric oxide synthase inhibitor, NMDA-induced cGMP formation was blocked, and the blockade of cGMP formation by L-NMMA (10 microM) could be reversed by simultaneous application of 1 mM arginine in both control and HI cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intrauterine hypoxia-ischemia increases N-methyl-D-aspartate-induced cGMP formation and glutamate accumulation in cultured rat cerebellar granule cells. 747 86

Nitric oxide (NO) is a novel biologic messenger with diverse effects but its role in organ transplantation remains poorly understood. Using a porphyrinic microsensor, the first direct measurements of coronary vascular and endocardial NO production were made. NO was measured directly in the effluent of preserved, heterotopically transplanted rat hearts stimulated with L-arginine and bradykinin; NO concentrations fell from 2.1 +/- 0.4 microM for freshly explanted hearts to 0.7 +/- 0.2 and 0.2 +/- 0.08 microM for hearts preserved for 19 and 38 h, respectively. NO levels were increased by SOD, suggesting a role for superoxide-mediated destruction of NO. Consistent with these data, addition of the NO donor nitroglycerin (NTG) to a balanced salt preservation solution enhanced graft survival in a time- and dose-dependent manner, with 92% of hearts supplemented with NTG surviving 12 h of preservation versus only 17% in its absence. NTG similarly enhanced preservation of hearts stored in University of Wisconsin solution, the clinical standard for preservation. Other stimulators of the NO pathway, including nitroprusside, L-arginine, or 8-bromoguanosine 3',5' monophosphate, also enhanced graft survival, whereas the competitive NO synthase antagonist NG-monomethyl-L-arginine was associated with poor preservation. Likely mechanisms whereby supplementation of the NO pathway enhanced preservation included increased blood flow to the reperfused graft and decreased graft leukostasis. NO was also measured in endothelial cells subjected to hypoxia/reoxygenation and detected based on its ability to inhibit thrombin-mediated platelet aggregation and serotonin release. NO became undetectable in endothelial cells exposed to hypoxia followed by reoxygenation and was restored to normoxic levels on addition of SOD. These studies suggest that the NO pathway fails during preservation/transplantation because of formation of oxygen free radicals during reperfusion, which quench available NO. Augmentation of NO/cGMP-dependent mechanisms enhances vascular function after ischemia and reperfusion and provides a new strategy for transplantation of vascular organs.
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PMID:Cardiac preservation is enhanced in a heterotopic rat transplant model by supplementing the nitric oxide pathway. 751 95

The objective of this study was to assess the cardioprotective effect of the nitric oxide (.NO) donor, S-nitrosoglutathione (GSNO) and to investigate the mechanism of cardioprotection in a model of ischemia and reperfusion in isolated rat hearts. The role of .NO in myocardial protection was investigated by using nitronyl nitroxide as the .NO trap. Electron spin resonance spectroscopy was used to demonstrate that nitronyl nitroxide can trap .NO released from GSNO in a cardioplegic solution. .NO traps, oxyhemoglobin (4 mumol/l, n = 4) and nitronyl nitroxide (400 mumol/l, n = 5), inhibited the (2 mumol/l) GSNO-induced coronary vasodilation from the control value of 122% (n = 6) above base-line value to 73 and 60%, respectively. In the ischemia-reperfusion protocol, GSNO (20 mumol/l) was added to the cardioplegic solution during a 35-min ischemic arrest (n = 8). GSNO improved the functional recovery of ischemic hearts as compared to control (n = 6) as measured by the developed pressure (76 +/- 3 to 95 +/- 5% of base-line), rate pressure product (68 +/- 3 to 83 +/- 4% of base-line) and diastolic pressure (31 +/- 2 to 19 +/- 3 mm Hg). Reduction of coronary flow rate during reperfusion to control values in GSNO-treated hearts did not eliminate the improvement of functional recovery induced by GSNO. GSNO increased cyclic GMP production and slowed the accumulation of lactate (154 +/- 7 in control to 114 +/- 4 mumol/g dry wt.) and glucose-6-phosphate (3.66 +/- 0.19 in control to 2.18 +/- 0.10 mumol/g dry wt.) in myocardial tissue during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:S-nitrosoglutathione improves functional recovery in the isolated rat heart after cardioplegic ischemic arrest-evidence for a cardioprotective effect of nitric oxide. 761

The hypothesis was tested that plasma from ischemic hindlimbs facilitates hypertension. Ischemia-induced hypertension was generated in rats by infrarenal aortic cross clamping for 5 h after which plasma was obtained from femoral vein blood. In vitro contractile activity of naive aortic rings incubated for 2 h in plasma collected from ischemic rats demonstrated reduced relaxation to acetylcholine and nitroglycerin. Methylene blue (10(-5) M) induced greater contraction in rings incubated in control vs. ischemic plasma, suggesting that endogenous guanylate cyclase activity is decreased by ischemic plasma. However, 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP) relaxed equally strips incubated in ischemic or control plasma. Acetylcholine-induced nitrite release was significantly lower in ischemic vs. control plasma-incubated strips (8.6 +/- 2.7 vs. 28.2 +/- 2.3 ng/10 mg tissue wt, respectively). The impaired relaxation to acetylcholine in ischemic plasma-incubated rings was significantly increased by L-arginine but not by prior treatment of ischemic plasma with heating or superoxide dismutase and catalase. These findings suggest the impaired relaxation is mediated through inhibition of the nitric oxide-cGMP pathway. Prolonged blunting of vasodilation by ischemic plasma may therefore contribute to maintenance of a sustained vasoconstriction and ischemic hypertension.
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PMID:Inhibition of vascular nitric oxide-cGMP pathway by plasma from ischemic hindlimb of rats. 763 55

We hypothesized that a decrease in cyclic GMP, a second messenger in the glutamate-nitric oxide pathway, would reduce oxygen consumption and improve O2 balance in the ischaemic cerebral cortex. To test this hypothesis, a study was performed in unilateral middle cerebral artery occluded rats which were assigned to either a control or methylene blue (10(-3) M) group. Regional cerebral blood flow was determined using 14C-iodoantipyrine and regional arterial and venous O2 saturations were determined by microspectrophotometry (n = 6). Cyclic GMP level was measured by radioimmunoassay (n = 8). Guanylate cyclase and cyclic GMP-phosphodiesterase activities were determined in an additional set of control rats (n = 10). The cyclic GMP levels were not different between the ischaemic and contralateral areas in the control group. Compared to the cyclic GMP in the control ischaemic cortex, topical methylene blue significantly decreased the cyclic GMP level by 56% in the ischaemic cortex of the methylene blue group. Ischaemia did not alter the activities of guanylate cyclase but mildly decreased cyclic GMP-phosphodiesterase. The regional cerebral blood flow and O2 consumption in the control group were 50% and 32% lower than those in corresponding contralateral cortex. Topical methylene blue did not alter regional cerebral blood flow and O2 consumption in the ischaemic cortex. Our data showed that cyclic GMP is not a major controller on O2 supply or O2 consumption in the ischaemic brain.
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PMID:Effects of topical methylene blue on cyclic GMP level, blood flow, and O2 consumption in focal cerebral ischaemia. 770 36

The cardioprotective effect of angiotensin-converting enzyme (ACE) inhibitors in cardiac ischemia/reperfusion damage is assumed to result largely from inhibition of the enzymatic breakdown of endogenous bradykinin (BK). We assessed the role of nitric oxide (NO) in mediating the beneficial actions of BK and the possible mechanism of the effect of NO. We experimentally infringed myocardial function in a working guinea pig heart preparation by ischemia (15 min) and reperfusion. The parameter external heart work (EHW), determined before and after ischemia, served as criterion for quantitation of recovery. We assessed oxidative stress during reperfusion by measuring glutathione release in coronary venous effluent; lactate release was used as a measure of ischemic challenge. The principal ability of NO to scavenge oxygen radicals was separately investigated in a chemiluminescence (CL) assay with the NO-donor sodium nitroprusside (SNP) and lucigenin. The ACE inhibitor ramiprilat (RT 25 microM) improved postischemic function significantly (55% recovery of EHW vs. 29% for controls). BK 1 nM was even more cardioprotective (71% recovery). The NO-synthase inhibitor Ng-nitro-L-arginine (NOLAG 10 microM) inhibited the effects of RT and BK (18% recovery each). SNP (0.3 microM) improved recovery to 57%, the prostacyclin analogue iloprost (ILO, 0.1 and 3 nM) had no beneficial effect (21 and 20% recovery, respectively). With 8-bromo-cyclicGMP, a membrane-permeable cGMP analogue, function was not better than control (30% recovery). Release of glutathione during reperfusion was decreased by the three compounds known to increase NO concentration in the heart; lactate release was the same in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide accounts for postischemic cardioprotection resulting from angiotensin-converting enzyme inhibition: indirect evidence for a radical scavenger effect in isolated guinea pig heart. 776 10

Changes of cGMP content in the rat brain and plasma have been evaluated by means of the radioimmunologic method after 5-min clinical death and up to 2 hours after resuscitation. Ischemia produced a decrease of cGMP in the brain, however, at the 15th min after resuscitation a reversible significant rise of nucleotide concentration was noted. In plasma at the end of ischemia and in the postischemic period a significant decrease of cGMP level was observed. The mechanisms of cGMP regulation in the central nervous system and the significance of the obtained results are discussed.
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PMID:Cyclic GMP levels in the rat brain and plasma during clinical death and after resuscitation. 779 9

Cardiac anaphylaxis, an acute ischemic dysfunction comprising coronary vasoconstriction and arrhythmias, is a model of clinically recognized immediate hypersensitivity reactions affecting the heart. Bradykinin, a mediator of hypersensitivity, is also a potent coronary vasodilator, acting via nitric oxide and prostacyclin production. Because ischemia increases bradykinin outflow from the heart, we questioned whether bradykinin might mitigate anaphylactic coronary vasoconstriction. Antigen challenge of hearts isolated from presensitized guinea pigs was associated with an approximately 30% increase in bradykinin overflow. Furthermore, (1) when the half-life of bradykinin was prolonged with the kininase II/angiotensin-converting enzyme inhibitors captopril and enalaprilat, anaphylactic coronary vasoconstriction was attenuated and reversed, and arrhythmias were alleviated; (2) the bradykinin B2-receptor antagonist HOE 140 prevented these effects; and (3) HOE 140 exacerbated both anaphylactic coronary vasoconstriction and arrhythmias. During cardiac anaphylaxis, the coronary overflow of cGMP, a marker of nitric oxide production, and 6-ketoprostaglandin F1 alpha, a stable prostacyclin metabolite, increased two-fold and fourfold, respectively. Because neither enalaprilat nor HOE 140 affected these changes, the enhanced overflow of cGMP and 6-ketoprostaglandin F1 alpha is likely to reflect the actions of other hypersensitivity mediators (eg, histamine and leukotrienes). We postulate that bradykinin plays a protective role in cardiac anaphylaxis by accumulating at the luminal surface of the coronary endothelium and promoting, in an autocrine mode, a B2-receptor-mediated production of nitric oxide and prostacyclin in concentrations sufficient to elicit a paracrine effect on coronary vascular smooth muscle, thus opposing the vasoconstricting effects of other anaphylactic mediators.
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PMID:Protective role of bradykinin in cardiac anaphylaxis. Coronary-vasodilating and antiarrhythmic activities mediated by autocrine/paracrine mechanisms. 785 89

By means of the radioimmunologic method changes of ANP content in the rat brain and plasma have been evaluated during 5-min clinical death and up to 2 hr after resuscitation. Ischemia did not produce significant rise of ANP immunoreactivity in the brain, however, in the early postresuscitation period its reversible increase was noted with the peak value at 15th min. The content of peptide in plasma significantly increased at the end of clinical death and 5 min after resuscitation. The obtained results can support the notion of quantitative relationship between concentration of ANP and cGMP content in the brain in vivo.
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PMID:Atrial natriuretic peptide in the rat brain and plasma during clinical death and after resuscitation. 792 98

Platelets have been implicated in the pathophysiology of ischemia-reperfusion injury. In this study, antiplatelet effects of cyclic GMP (cGMP)- and cyclic AMP (cAMP)-mediated agents were evaluated in renal ischemia in pentobarbital-anesthetized rats. Renal ischemia was induced by unilateral occlusion of the left renal artery (40 min) followed by reperfusion (30 min) with the contralateral kidney serving as control. 111Indium-labeled platelets, drugs or vehicle were administered 30 min before induction of renal ischemia. Occlusion of the left renal artery for 20, 40 or 60 min resulted in a 100, 300 and 600% increase (over contralateral right kidney) in the platelet-associated 111indium activity in the ischemic kidney. In all subsequent studies the kidney was occluded for 40 min to test the antiplatelet activity of individual agents. 8-Br-cGMP (0.1 and 0.3 mg/kg/min i.v.), zaprinast (0.1 mg/kg/min i.v.) and sodium nitroprusside (0.003 and 0.01 mg/kg/min i.v.) significantly attenuated platelet accumulation in renal ischemia, whereas 8-Br-cAMP (0.3 mg/kg/min i.v.) or milrinone (0.1 mg/kg i.v. bolus, plus 0.01 mg/kg/min) did not. Minoxidil (0.01 and 0.03 mg/kg/min i.v.), a vasodilator which produced equihypotensive effects as the cGMP-mediated agents, and milrinone failed to prevent platelet accumulation. These results demonstrate that modulation of the platelet function by cGMP agents can be dissociated from their blood pressure lowering effects. cGMP is known to inhibit both platelet adhesion and aggregation, whereas cAMP is only active against aggregation. The present findings provide further evidence that cGMP-mediated drugs may afford effective antiplatelet action in an in vivo model of ischemia-reperfusion injury.
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PMID:Cyclic GMP but not cyclic AMP prevents renal platelet accumulation after ischemia-reperfusion in anesthetized rats. 799 27


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