UMLS:C0022116 - FACTA Search

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

Prior induction of heat shock protein 70 (HSP70) protects against ischemia-reperfusion (I/R) mucosal injury, but the ability of HSP70 to affect I/R-induced alterations in epithelial cell function is unknown. Rats subjected to whole body hyperthermia (41.5-42 degrees C for 6 min) increased HSP70 and heat shock factor 1 mRNA expression, reaching a maximum 2 h after heat stress and declining thereafter. HSP70 production was maximally elevated at 4 h after heat stress and remained elevated until after 12 h. Heat stress alone had no effect on mucosal function except to enhance secretion in response to ACh. Heat stress provided complete morphological protection against I/R-induced mucosal injury but did not confer a similar protection against I/R-induced decreases in mucosal resistance, sodium-linked glucose absorption, or tachykinin-mediated chloride secretion. Heat stress, however, attenuated the I/R-induced suppression of ACh response, and this effect was dependent on enteric nerves. Thus induction of heat shock protein 70 is associated with the preservation of mucosal architecture and attenuation of some specific functional alterations induced by I/R.
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PMID:Heat stress protection against mesenteric I/R-induced alterations in intestinal mucosa in rats. 1201 79

Conflicting data are available regarding the acute effect of exercise-provoked leg ischemia on the endothelial function in patients with stage II peripheral artery disease (PAD). In order to clarify this issue, cutaneous hyperemic responses to iontophoresis delivery of an endothelium-dependent (acetylcholine, ACh) and an endothelium-independent (sodium nitroprusside, SNP) vasodilator were evaluated under resting conditions, and before and after a treadmill test, using laser Doppler flowmetry, in 14 males (aged 68 +/- 4 years) affected by stage II PAD; 14 age-matched healthy males served as controls. At resting, a significantly reduced skin hyperemic response to ACh and to SNP was observed in PAD patients when compared to controls. Following treadmill, the leg skin hyperemic response to ACh delivery was significantly lower at peak of claudication than prior exercise (139 +/- 10 vs 213 +/- 25%, P = 0.01) in PAD patients, whereas no difference was observed in controls. The hyperemic response to SNP after exercise did not differ from baseline in either PAD patients or controls. The present data are in keeping with a reduced skin vasodilator capacity in stage II PAD patients at resting. In addition, the further impairment of skin endothelium-dependent vasodilation at the peak of claudication could indicate an acute endothelial dysfunction associated with exercise-induced leg muscle ischemia. These preliminary results also suggest that the threshold of claudication should not be exceeded during rehabilitation programs for PAD patients.
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PMID:Acute effect of exercise-induced leg ischemia on cutaneous vasoreactivity in patients with stage II peripheral artery disease. 1207 26

We hypothesized that myocardial contractile function and coronary arterial function are greater after ischemia and reperfusion in high-intensity treadmill-trained vs. sedentary rats. Rats performed 10 x 4-min bouts of treadmill running consisting of 2 min at 13 m/min + 2 min at 45-60 m/min (Etr) or were sedentary (Sed) for 12 wk. Animals then were instrumented to measure left ventricular (LV) contractility in response to three 15-min coronary occlusion (O) and 5-min reperfusion (R) cycles (Isc) or a sham operation (Sham). After the Isc and Sham protocols, hearts were excised and coronary arterial ( approximately 105 microm ID) function was evaluated by using isometric techniques. LV developed pressure, the first derivative of LV pressure at a developed pressure of 40 mmHg, and systolic blood pressure were not different between Etr (n = 14) and Sed (n = 7) rats before or after the Sham protocol. Furthermore, hemodynamic variables were similar in Etr (n = 14) and Sed (n = 13) animals before the Isc protocol and were depressed to the same degree by the three O-R cycles. Therefore, Etr did not alter myocardial contractile function in rats that were (i.e., Isc) or were not (i.e., Sham) exposed to ischemia and reperfusion. Acetylcholine-evoked relaxation (10-8 to 3 x 10-5 M) was greater (P < 0.05) in coronary arteries from Sham-Etr vs. Sham-Sed animals (5 of 8 doses tested) and Isc-Etr vs. Isc-Sed rats (3 of 8 doses tested). Maximal relaxation produced by sodium nitroprusside (10-4 M) was similar among groups. Vasocontractile responses produced by KCl (10-100 mM) and endothelin-1 (10-11-10-4 M) were greater (P < 0.05) in the presence vs. the absence of nitric oxide synthase inhibition (10-6 M NG-monomethyl-l-arginine) in vessels from Sham-Etr but not Sham-Sed rats and from Isc-Etr but not Isc-Sed rats. These findings suggest that Etr-evoked improvements in coronary function are maintained in small arteries even when exposed to ischemia and reperfusion.
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PMID:Improved coronary vascular function evoked by high-intensity treadmill training is maintained in arteries exposed to ischemia and reperfusion. 1281 13

Placental ischemia during pregnancy is associated with increased plasma cytokines such as interleukin-6 (IL-6), which may contribute to increased vascular resistance and hypertension of pregnancy. We tested the hypothesis that an increase in plasma IL-6 during pregnancy is associated with impaired endothelium-dependent relaxation, enhanced vascular contraction, and hypertension. Systolic blood pressure was measured in virgin and pregnant Sprague-Dawley rats non-treated or infused with IL-6 (200 ng/kg per day for 5 days). Isometric contraction was measured in isolated aortic strips, and endothelial nitric oxide (NO) synthase (eNOS) was measured in aortic homogenate using Western blots. Blood pressure was greater in IL-6-infused (146+/-3) than in control pregnant rats (117+/-2 mm Hg). In endothelium-intact vascular strips, phenylephrine (Phe) caused greater increase in active stress in IL-6-infused (maximum: 10.6+/-0.6) than in control pregnant rats (maximum: 4.1+/-0.3x10(4) N/m2). Acetylcholine (ACh)-induced relaxation of Phe contraction and vascular eNOS protein and nitrite/nitrate production were less in IL-6-infused than in control pregnant rats. N(omega)-nitro-L-arginine methyl ester (10(-4) mol/L), inhibitor of NOS, or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (10(-5) mol/L), inhibitor of cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in control but not IL-6-infused pregnant rats. Endothelium removal enhanced Phe-induced stress in control but not in IL-6-infused pregnant rats. The blood pressure and vascular Phe-induced contraction, ACh relaxation, and eNOS protein were not different between control and IL-6-infused virgin rats. Thus, an endothelium-dependent NO-cGMP-mediated relaxation pathway is inhibited in systemic vessels of pregnant rats infused with IL-6. The results support a role for IL-6 as a possible mediator of the increased vascular resistance during hypertension of pregnancy.
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PMID:Reduced endothelial NO-cGMP-mediated vascular relaxation and hypertension in IL-6-infused pregnant rats. 1470 55

In the rabbit heart, bradykinin and ACh trigger preconditioning by a mechanism involving ATP-sensitive potassium channel-dependent production of reactive oxygen species (ROS). Recent evidence indicates that the pathway by which bradykinin causes ROS generation includes nitric oxide synthase (NOS) and protein kinase G (PKG). On the other hand, Akt was shown to be essential for ACh to generate ROS. This study determines whether these two G-coupled receptor agonists indeed have similar signaling targets, i.e., whether Akt is involved in bradykinin's pathway and whether NOS is involved in ACh's pathway. Isolated adult rabbit cardiomyocytes were incubated for 15 min in reduced MitoTracker red, which becomes fluorescent only after exposure to ROS. Bradykinin (400 nM) and ACh (250 microM) caused a 51.4 +/- 14.8% and 39.8 +/- 11.7% increase, respectively, in ROS production (P <0.005). Coincubation of either agonist with Akt inhibitor (20 microM) or infection of cells with an adenovirus containing dominant negative Akt abolished this increase. The NO donor S-nitroso-N-acetyl penicillamine (SNAP, 1 microM) also increased the ROS signal by 40.8 +/- 15.7%, but this increase was unaffected by Akt inhibitor (39.0 +/- 6.4%), implying that Akt is upstream of NOS. ACh-induced ROS production could be abolished by either of the NOS inhibitors Nomega-monomethyl-L-arginine monoacetate (100 microM) and L-N5-(1-iminoethyl)ornithine hydrochloride (L-NIO, 5 microM). L-NIO also blocked the anti-infarct effect of ACh (550 microM) in isolated rabbit hearts exposed to 30 min of regional ischemia. We conclude that both bradykinin and ACh trigger ROS generation by sequentially activating Akt and NOS.
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PMID:Acetylcholine and bradykinin trigger preconditioning in the heart through a pathway that includes Akt and NOS. 1533 66

Acetylcholine (ACh) and bradykinin (BK) are potent pharmacological agents which mimic ischemic preconditioning (IPC) enabling hearts to resist infarction during a subsequent period of ischemia. The cardioprotective pathways activated by BK but not ACh may also protect when activated at reperfusion. ACh and BK stimulate Gi/o-linked receptors and ultimately mediate protection by opening mitochondrial ATP-sensitive potassium channels with the generation of reactive oxygen species that act as second messengers to activate protein kinase C (PKC). There appear to be key differences, however, in the pathways prior to potassium channel opening for these two receptors. This review aims to summarize what is currently known about pharmacological preconditioning by ACh and BK with an emphasis on differences that are seen in the signal transduction cascades. Understanding the cellular basis of protection by ACh and BK is a critical step towards developing pharmacological agents that will prevent infarction during ischemia resulting from coronary occlusion or heart attack.
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PMID:Mechanisms of acetylcholine- and bradykinin-induced preconditioning. 1592 53

Cytochrome p450 (CYP) inhibitors provide protection against myocardial infarction following both global and focal cardiac ischemia and reperfusion (I/R). We hypothesized that sulfaphenazole, an inhibitor of CYP2C6 and 9, also attenuates post-ischemic endothelial dysfunction by reducing CYP-mediated superoxide generation (which scavenges nitric oxide (NO)), thereby restoring NO bioavailability and vascular tone. Rat hearts were perfused in the Langendorff mode for 20 min in the presence, or absence, of sulfaphenazole and then subjected to 30 min global no-flow ischemia followed by 15 min reperfusion. Septal coronary resistance arteries were isolated and mounted on glass cannulae for measurements of luminal diameter. Preconstricted arteries were exposed to acetylcholine to elicit endothelium-dependent, NO-mediated vasodilation. Acetylcholine caused near maximal dilation in control tissues not subjected to I/R. Following I/R, endothelium-dependent vasodilation was reduced. Pretreatment with sulfaphenazole restored endothelial sensitivity to acetylcholine. Vasoresponsiveness to endothelium-independent vasodilators, sodium nitroprusside and isoproterenol, were also reduced following I/R. However, sensitivity to endothelium-independent vasodilators was not restored by pretreatment with sulfaphenazole. I/R-induced superoxide production was assessed by dihydroethidium staining of flash frozen hearts. Sulfaphenazole treatment significantly reduced superoxide production in arterial walls following I/R injury. We conclude that sulfaphenazole restores post-ischemic endothelium-dependent, NO-mediated vasodilation by reducing superoxide production, suggesting that CYP2C9 plays a key role in post-ischemic vascular dysfunction.
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PMID:Cytochrome p450 2C inhibition reduces post-ischemic vascular dysfunction. 1615 Jun 54

We have previously shown using a water maze task that transient 2 vessel occlusion (T2VO) induced learning deficit in mice and that the deficit was prevented by pre-treatment of mice with chotosan, a Kampo prescription. In this study, we investigated the mechanism underlying the preventive effect of chotosan on T2VO-induced learning deficit. Chotosan administration 1 h before T2VO operation prevented learning impairment. The extract of Uncaria, a major constituent of chotosan, also had a protective effect on learning impairment in T2VO mice, whereas Uncaria-free chotosan had no beneficial effect on maze performance of T2VO mice. The ameliorative effect of chotosan was blocked by pirenzepine, a muscarinic M1 antagonist, but not by mecamylamine, a nicotinic receptor antagonist. Acetylcholine (ACh) content in the hippocampus of T2VO mice was significantly lower than that in the hippocampus of sham-operated control mice. Chotosan and Uncaria administration attenuated T2VO-induced reduction of ACh levels in the brain. These results suggest that the preventive effect of chotosan on transient ischemia-induced learning impairment is mainly attributable to the effect of Uncaria and that the ameliorative effect is mediated by stimulation of muscarinic M1 receptor.
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PMID:Preventive effect of chotosan, a Kampo medicine, on transient ischemia-induced learning deficit is mediated by stimulation of muscarinic M1 but not nicotinic receptor. 1620 38

Acetylcholine (ACh) and opioid receptor agonists trigger the preconditioned phenotype through sequential activation of the epidermal growth factor (EGF) receptor, phosphatidylinositol 3-kinase (PI3-K), Akt, and nitric oxide synthase (NOS), and opening of mitochondrial (mito) K(ATP) channels with the generation of reactive oxygen species (ROS). Although extracellular signal-regulated kinase (ERK) has recently been reported to be part of this pathway, its location has not been determined. To address this issue, we administered a 5-min pulse of ACh (550 microM) prior to 30 min of ischemia in isolated rabbit hearts. It reduced infarction from 30.4 +/- 2.2% of the risk zone in control hearts to 12.3 +/- 2.8% and co-administration of the MEK, and, therefore, downstream ERK inhibitor U0126 abolished protection (29.1 +/- 4.6% infarction) con.rming ERK's involvement. MitoK(ATP) opening was monitored in adult rabbit cardiomyocytes by measuring ROS production with MitoTracker Red. ROS production was increased by each of three G protein-coupled agonists: ACh (250 microM), bradykinin (BK) (500 nM), and the delta-opioid agonist DADLE (20 nM). Co-incubation with the MEK inhibitors U0126 (500 nM) or PD 98059 (10 microM) blocked the increased ROS production seen with all three agonists. Direct activation of its receptor by EGF increased ROS production and PD 98059 blocked that increase, thus placing ERK downstream of the EGF receptor. Desferoxamine (DFO) which opens mitoK(ATP) through direct activation of NOS also increased ROS. PD 98059 could not block DFO-induced ROS production, placing ERK upstream of NOS. In isolated hearts, ACh caused phosphorylation of both Akt and ERK. U0126 blocked phosphorylation of ERK but not of Akt. The PI3-K inhibitor wortmannin blocked both. Together these data indicate that ERK is located between Akt and NOS.
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PMID:Localizing extracellular signal-regulated kinase (ERK) in pharmacological preconditioning's trigger pathway. 1628 91

Growth hormone and IGF-1 have been suggested to have tissue-protective effects. Ghrelin is a stomach-derived growth hormone secretagogue. The effects of ghrelin on ischemia/reperfusion-induced renal failure in mice were examined. Ischemic acute renal failure was induced by bilateral renal artery clamping for 45 min and reperfusion for 24 h. Ghrelin (100 microg/kg mouse) or vehicle was injected subcutaneously six times before surgery and three times after surgery every 8 h. Twenty-four hours after reperfusion, the right kidney was isolated and perfused. Acetylcholine (ACh)- and adrenomedullin-induced endothelium-dependent vasorelaxation of renal vessels significantly improved in ghrelin-pretreated mice (%Delta renal perfusion pressure by 10(-7) M ACh -63.5 +/- 3.7 versus -41.2 +/- 5.5%; P < 0.05). This change was associated with significant increases of nitric oxide release in the kidneys of ghrelin-treated mice (10(-7) M ACh 35.5 +/- 5.8 versus 16.9 +/- 3.5 fmol/g kidney per min; P < 0.05). Serum concentration of urea nitrogen (53 +/- 7 versus 87 +/- 15 mg/dl; P < 0.05) and renal injury score were significantly lower in the ghrelin group (2.5 +/- 0.8 versus 5.3 +/- 1.5; P < 0.01). Tubular apoptotic index was significantly lower in the ghrelin group (5 +/- 5 versus 28 +/- 4; P < 0.05). Furthermore, the survival rate after the 60-min ischemic period was higher in the ghrelin group (80 versus 20%; P < 0.05). Ghrelin treatment significantly increased the serum level of IGF-1. However, such renal protective effects of ghrelin on ischemia/reperfusion injury were not observed in insulin receptor substrate-2 knockout mice. These results suggest that ghrelin may protect the kidneys from ischemia/reperfusion injury and that this effect is related to an improvement of endothelial function through an IGF-1-mediated pathway.
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PMID:Ghrelin improves renal function in mice with ischemic acute renal failure. 1630 69

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