Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vascular effects of tirilazad mesylate (U-74006F), a 21-aminosteroid antioxidant under development for the treatment of acute CNS trauma and ischemia, have been investigated using isolated rings of rabbit aorta. Endothelium-dependent relaxation was measured in rings contracted with 0.25 microM phenylephrine. Acetylcholine produced a dose-dependent relaxation that was slightly attenuated by the addition of U-74006F (0.1-10.0 microM). At a concentration of 10.0 microM, U-74006F shifted the EC50 for acetylcholine relaxation from 60 +/- 10 to 150 +/- 20 nM and reduced the maximum response by 20%. U-74006F (0.1-10.0 microM), did not reduce relaxation to the endothelium-independent vasodilator nitroglycerin nor did it affect the tone of either resting or phenylephrine contracted rings. ACh relaxation was abolished by a 40 min treatment with the superoxide generating system xanthine oxidase (XO; 0.1 U/ml) plus xanthine (0.4 mM). Relaxation to nitroglycerin was not impaired by XO, nor were the phenylephrine-induced contractions. U-74006F, at doses of 0.05-10 microM, protected against XO mediated damage to endothelium-dependent relaxation. These results demonstrate that tirilazad mesylate can protect endothelial function from damage by reactive oxygen species. Preservation of endothelial function might represent an important component of the activity of tirilazad mesylate in vivo.
 ...
PMID:Vascular effects of the 21-aminosteroid tirilazad mesylate: protection against oxidant stress. 747 15

Concentrations of acetylcholine and the monoaminergic neurotransmitters dopamine, serotonin and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxy-phenylacetic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA) and choline were simultaneously determined in the corpus striatum of rats after 15 min. complete cerebral ischemia (CCI) and in different intervals (1, 24, 48, 72, 96 hours) of postischemic cerebral reperfusion. Results were compared to respective sham-operated control animals. After 15 min. CCI acetylcholine concentration decreased to 15%, and dopamine concentration to 56% of the control values. The metabolite levels of DOPAC decreased to 40% and HVA to 64% of the control values. Acetylcholine, dopamine, serotonin and choline concentrations were not changed significantly after reperfusion. The metabolites HVA and 5-HIAA showed their maximum increases after 1 and 24 hours of reperfusion, additionally HVA was decreased both, after 72 and 96 hours of reperfusion. The data indicate that surprisingly little permanent damage could be caused by a 15 min. ischemia in the striatum. Tissue levels of the neurotransmitters appeared differentially altered but similarly regulated during ischemia and subsequent recirculation. Acetylcholine and dopamine levels decreased profoundly during ischemia. However, acetylcholine levels could be compensated rapidly during reperfusion, whereas the dopaminergic system showed a long-lasting change in its turnover rate. Although serotonin levels were unaffected by CCI, there was an increase of its presumed turnover rate during reperfusion.
 ...
PMID:Effects of long-term recovery from transient cerebral ischemia in rat brain: tissue levels of acetylcholine, monoamines, and their metabolites. 750 89

We studied the effect of ischaemia and reperfusion on vasoconstrictor and vasodilator mechanisms. Anaesthetized rabbits were subjected to 4-h abdominal aortic occlusion and 1-h reperfusion in vivo. Segments of the abdominal (ischaemic-reperfused) and thoracic (control) aorta were then removed for in vitro studies. Ischaemia/reperfusion had no significant effect on relaxant responses to either acetylcholine (ACh:endothelium-dependent) or sodium nitroprusside (SNP:endothelium-independent). The sensitivity of the aorta to contraction by phenylephrine was significantly increased in aortic rings with or without endothelium (by 2.2- and 3.7-fold, respectively), but was not different after 4-h ischaemia without reperfusion. In contrast, responses to methoxamine, serotonin, and U46619 were not affected by ischaemia/reperfusion. Moreover, the relative increase in aortic sensitivity to phenylephrine was prevented by treatment of control and ischaemic-reperfused aortic rings with the neuronal uptake inhibitor cocaine (10(-5) M). These results suggest that after 4-h ischaemia, reperfusion damages sympathetic neuronal uptake mechanisms in rabbit aorta. As a result, phenylephrine, an agonist normally susceptible to neuronal uptake, may exert more potent contractile effects. Endothelium-dependent and endothelium-independent relaxant mechanisms in the aorta appear to be resistant to acute ischaemia and reperfusion.
 ...
PMID:Ischaemia/reperfusion enhances phenylephrine-induced contraction of rabbit aorta due to impairment of neuronal uptake. 751 5

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.
 ...
PMID:Inhibition of vascular nitric oxide-cGMP pathway by plasma from ischemic hindlimb of rats. 763 55

1. Cerebral ischemia of 5 min duration was induced in unanesthetized gerbils by bilateral occlusion of the carotid arteries. 2. The extent of cerebral damage was assessed by the elevation of motor activity in comparison with control animals and by a histological assessment of the extent of neuronal degeneration in the CA1 area of the hippocampus. 3. Atropine, an antagonist of ACh, at either a low (1 mg/kg) or a high (10 mg/kg) dose administered 15 min prior to the ischemic episode, did not confer protection against cerebral ischemic damage. 4. This finding suggests that ACh does not play a critical role in the generation of ischemia reperfusion injury.
 ...
PMID:Atropine and cerebral ischemic injury in the Mongolian gerbil. 795 34

The ATP-sensitive potassium channel (K+ATP channel) is known to exist in blood vessels and to regulate vascular tone. We examined the role of this channel in coronary arteriolar vasomotion during coronary autoregulation, ischemia, reactive hyperemia and endothelium-dependent response by acetylcholine in vivo. Experiments were performed with anesthetized open-chest dogs. Coronary arterioles were directly observed in situ by means of a floating objective system or a stroboscopic epi-illumination system synchronized with cardiac motion. Small arterioles less than 100 microns in internal diameter dilated in response to reduction in perfusion pressure (perfusion pressure: 60, 40, 25 mm Hg). Glibenclamide, a selective blocker of the K+ATP channel, reversed the dilation. Reactive hyperemia produced by 20-second occlusion of the left anterior descending coronary artery resulted in arteriolar dilation, the magnitude of which was greater in smaller arterioles than in larger ones. Glibenclamide significantly inhibited the dilation in both large and small arterioles. Acetylcholine (ACh) produced dilation in arterioles of all sizes. NG-monomethyl L-arginine, a competitive inhibitor of nitric oxide synthesis, abolished the dilation of large arterioles, but failed to abolish the dilation in small arterioles. Glibenclamide, however, did not have any additional inhibitory effect on ACh-induced arteriolar dilation. Thus, we conclude that the K+ATP channel plays an important role in coronary microvascular vasomotion during autoregulation, ischemia and reactive hyperemia, but not during endothelium-dependent vasodilation induced by ACh in vivo.
 ...
PMID:The role of ATP-sensitive potassium channels in regulating coronary microcirculation. 818 3

Cerebral hypoxia-ischemia was produced in 7 day old rats by right common carotid artery occlusion combined with systemic hypoxia. In the hypoxic-ischemic group animals, striatal ACh contents on both sides were reduced to a significant extent in commensurate to AChE histochemical image analysis. All these changes could be restored to normal control by a protection dose (50 micrograms) of NGF intraventricularly injected.
 ...
PMID:[Protective effect of nerve growth factor on cholinergic neurons corpus striatum of new born rat subjected to hypoxia-ischemia]. 829 6

Acetylcholine (ACh) release into the extracellular space was measured by HPLC with electrochemical detection after in vivo intracerebral microdialysis in the striatum of gerbils subjected to 15 min of bilateral carotid artery occlusion followed by 5 h of recirculation. Tissue ACh and choline (Ch) contents were also determined during ischemia and after 5, 30, 60, and 120 min of reflow. Fifteen minutes of ischemia led to a significant transient increase in extracellular ACh concentration (threefold after 7.5 min of ischemia) concomitant with a reduced endogenous ACh level (-62%) and increased tissue Ch content (ninefold). Recirculation significantly reduced the ACh release during the early period of reflow (-50% vs. basal level), followed by a significant increase in ACh release between 1 and 3 h of reflow (45-55% vs. basal level) and subsequent normalization. Simultaneously, a "rebound" of tissue ACh level occurred in the early period of reflow (fourfold vs. ischemic value), followed by gradual normalization after 2 h of reperfusion, whereas a rapid decrease in tissue Ch levels was found after 30 min of reflow. These findings represent the first demonstration of a biphasic release of ACh during ischemia and reperfusion, as assessed by intracerebral microdialysis in gerbils.
 ...
PMID:Biphasic striatal acetylcholine release during and after transient cerebral ischemia in gerbils. 836 Feb 85

The purpose of this study was to determine whether warm ischemia (WIT) and cold storage preservation (CSP) impair endothelium-dependent vascular relaxation in the kidney. Twenty-four canine kidneys were harvested, preserved with CSP for 24 or 48 hours, and then perfused with canine blood at 37 C for the determination of glomerular filtration rate (GFR), perfusion flow rate, and renal vascular resistance (RVR). There were four experimental groups: Group I--no WIT followed by 24 hours CSP, Group II--30 minutes WIT followed by 24 hours CSP, Group III--no WIT followed by 48 hours CSP, Group IV--30 minutes WIT followed by 48 hours CSP. Endothelial function in each group was evaluated using acetylcholine (ACh, 1 mg. bolus) as an endothelial dependent vasodilator, and sodium nitroprusside (NP, 10 mg. bolus) as an endothelial independent vasodilator. Glomerular filtration rate was significantly less (P < .05) and RVR was significantly greater (P < .05) for kidneys from Groups II, III and IV compared to group I. The highest RVR was observed in kidneys from Groups II and IV. Nitroprusside administration caused an equivalent reduction in RVR among all four study groups. ACh administration caused a similar reduction in RVR in Groups I and III; however, the change in RVR was significantly less in Groups II and IV (P < .05). We hypothesize that the more severe ischemic insult in the latter groups led to vascular endothelial damage with a consequent loss of ability to secrete endothelium-derived relaxing factor in response to ACh administration.
 ...
PMID:Renal vascular response to vasodilators following warm ischemia and cold storage preservation in dog kidneys. 841 7

This study examined the question of whether intracoronary administration of nitroglycerin modifies contralateral intracoronary acetylcholine test results. Acetylcholine was injected separately into both left and right coronary arteries in 63 patients with coronary spastic angina. Acetylcholine (20 and 50 micrograms) was injected first into the coronary artery responsible for the documented regional ischemia during spontaneous or induced attacks, and then into the other coronary artery. Coronary spasm was defined as severe transient coronary artery vasoconstriction with chest pain and/or electrocardiographic ischemic ST-segment deviation. Spasm was induced in either coronary artery in 60 patients (95%) and in both coronary arteries in 23 patients (37%). The frequency of induced spasm was 67% (42 of 63) in the coronary artery first challenged by acetylcholine. The coronary artery spasm subsided with the intracoronary injection of nitroglycerin (250-750 micrograms) in 19 patients. In the second challenge of intracoronary acetylcholine injection into the contralateral coronary artery, coronary spasm was induced in 29 (66%) of 44 patients. This was done without intracoronary administration of nitroglycerin in the first challenge and in 12 (63%) of 19 patients who had been given intracoronary nitroglycerin. The sensitivity for spasm induced by intracoronary acetylcholine appeared to be unaffected by nitroglycerin. Coronary spasm with ST-segment elevation by intracoronary acetylcholine in the second challenge was significantly less frequent in the patients receiving intracoronary acetylcholine in the second challenge was significantly less frequent in the patients receiving intracoronary nitroglycerin (first: 89%, second: 26%, p < 0.05) as well as in those not receiving intracoronary nitroglycerin for the spasm in the first challenge (first: 52%, second: 13%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of intracoronary administration of nitroglycerin on contralateral intracoronary acetylcholine test results. 844 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>