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)

Bifemelane hydrochloride (BF) is a modulator of various neurotransmitter systems. The effect of BF on the cholinergic system was studied in the gerbil hippocampus at 100 days after ischemic damage. Marked enhancement of AChE staining was noticed in the CA1 of saline-treated animals at 100 days after ischemia, while the post-ischemic enhancement of AChE staining intensity was milder in BF-treated animals. Muscarinic receptor density was markedly decreased in the CA1 subfield after ischemia. Interestingly, BF-treated animals showed higher muscarinic receptor binding in many brain areas, particularly in the dentate gyrus. These results indicate that BF modulates cholinergic neuronal plasticity in the ischemic hippocampus after long-term survival.
 ...
PMID:The effect of long-term post-ischemic bifemelane hydrochloride treatment on cholinergic systems in the gerbil hippocampus. 881 67

1. The aim of this study was to investigate whether global ischaemia and reperfusion in rat isolated hearts affects endothelium-dependent vasodilatation and adrenoceptor-mediated vasoconstriction. In addition, it was first determined whether inhibition of the actions of nitric oxide (NO) influenced the responses to alpha-adrenoceptor agonists in the rat coronary vasculature. 2. In rat isolated, Langendorff perfused hearts, inhibition of NO with haemoglobin (Hb, 6 microM) significantly inhibited the vasodilator responses to the endothelium-dependent vasodilators, acetylcholine (ACh, 3-100 pmol), carbachol (CCh, 10-300 pmol), bradykinin (Bk, 1-30 pmol) and histamine (0.3-10 nmol) but did not affect responses to the endothelium-independent vasodilator, sodium nitroprusside (SNP, 0.01-1 nmol). 3. Inhibition of the action of NO by Hb significantly enhanced the vasoconstrictor response to the non-selective alpha-adrenoceptor agonist, noradrenaline (NA, 0.1-10 nmol) and the alpha 2-adrenoceptor agonist, B-HT 920 (0.001-1 mumol) but had no effect on the vascular response to the alpha 1-adrenoceptor agonist, methoxamine (MTX, 10-300 nmol). 4. In the perfused hearts ischaemia, induced by 30 min perfusion at 5% of the normal rate of flow, followed by 15 min of reperfusion (ischaemia/reperfusion) selectively impaired the vasodilator responses to ACh and CCh which act by muscarinic receptor stimulation but did not affect responses to the other endothelium-dependent vasodilators Bk and histamine or to the endothelium-independent dilator SNP. 5. After ischaemia/reperfusion the coronary vasoconstrictor responses to B-HT 920 were slightly but significantly enhanced whereas the responses to NA and MTX were unaffected. 6. Thus, in the rat isolated heart, low flow induced-ischaemia and reperfusion causes a selective impairment of muscarinic receptor-mediated vasodilatation but does not impair responses to all endothelium-dependent vasodilators. Enhanced constrictor responses to noradrenaline and B-HT 920 in the presence of Hb indicates that endogenous NO modulates the constriction of coronary resistance vessels in response to stimulation of alpha 2-adrenoceptors. Ischaemia and reperfusion in this isolated vascular bed caused only a small increase in the coronary vasoconstrictor response to alpha 2-adrenoceptor stimulation. It appears that in the rat isolated heart the degree of endothelial dysfunction caused by ischaemia/reperfusion is insufficient to cause a functionally significant change in alpha-adrenoceptor-mediated constriction.
 ...
PMID:The effect of ischaemia on endothelium-dependent vasodilatation and adrenoceptor-mediated vasoconstriction in rat isolated hearts. 888 95

The effects of growth hormone (GH) deficiency on cardiac function were studied in young male rats administered an anti-GH-releasing hormone (GHRH) serum from postnatal day 20 to 40. Dependence of heart abnormalities on GH deficiency was ascertained by giving a group of anti-GHRH serum-treated rats GH replacement therapy. Heart preparations from anti-GHRH serum-treated rats, undergoing low-flow ischemia, showed a progressive increase in left ventricular end-diastolic pressure with poor recovery of mechanical activity and increased coronary perfusion pressure upon reperfusion. Hearts from anti-GHRH serum + GH-treated rats, undergoing global reduction to the flow, showed only a minimal increase of left ventricular end-diastolic pressure and, upon reperfusion, cardiac mechanical activity recovered almost completely. Similar findings were also observed in heart preparations from control (normal rabbit serum-treated) rats. Infusion of acetylcholine (10(-6) M) into heart preparations in the preischemic period increased coronary perfusion pressure values more markedly in hearts from normal rabbit serum- and anti-GHRH serum + GH-treated rats than in those from anti-GHRH serum-treated rats. These results indicate that selective GH deficiency in young male rats renders the heart more sensitive to ischemic damage and leads to an impairment of cardiac muscarinic receptor function.
 ...
PMID:Worsening of ischemic damage in hearts from rats with selective growth hormone deficiency. 895 55

We investigated the dynamics of the gene expression of the m1 subtype of muscarinic cholinergic receptor in the rat hippocampus following transient global ischemia. This receptor represents the dominant phosphoinositide linked muscarinic receptor in the hippocampus, and is recognized to modulate various aspects of neuronal activity in the hippocampus. Our results demonstrate that following severe transient global ischemia, m1 receptor expression is altered in the hippocampus in a time dependent manner. Expression levels declined in the dentate gyrus within 3 h of insult, reached minimal levels by 6 h, and then slowly recover to control levels. Expression levels in the CA1 and CA3 decreased as well, but did not reach minimal levels until 24 h post-insult. By day 3, expression levels in all regions except CA1, where vulnerable neurons began to drop out, had returned to control levels. These results demonstrate that transient alterations in the gene expression levels for the m1 muscarinic receptor occur in all subfields of the hippocampus following transient forebrain ischemia.
 ...
PMID:Cerebral ischemia alters the regional hippocampal expression of the rat m1 muscarinic acetylcholine receptor gene. 897 86

We examined the effect of Oren-gedoku-to (TJ15), which is a traditional herbal Kampo prescription used as an anti-cerebral apoplexy agent on these changes. Chronic pre- and post-ischemia TJ15 oral administration almost completely abolished the ischemia-induced muscarinic receptor reduction and 5-hydroxyindoleacetic acid level increase. These results suggest that TJ15 prevents cholinergic synaptic dysfunction and serotonergic presynaptic hyperactivity induced by transient ischemia.
 ...
PMID:Chronic administration of Oren-gedoku-to (TJ15) inhibits ischemia-induced changes in brain indoleamine metabolism and muscarinic receptor binding in the Mongolian gerbil. 902 59

Heparin has potential use as an antiinflammatory treatment in many lung diseases but its therapeutic use is limited by inherent anticoagulant activity. The anticoagulant nature of heparin can be eliminated by a number of chemical treatments, but often not without loss of other important pharmacological activities. Lyophilization of porcine mucosal heparin under extreme alkaline conditions (pH > or = 13) produces a nonanticoagulant heparin remarkable for the selective loss of only 2-O and 3-O sulfates, leaving 6-O and N-sulfates intact. In contrast to the commonly used nonanticoagulant analog N-desulfated, N-reacetylated heparin, selectively O-desulfated heparin retains potent activity as an inhibitor of the cationic neutrophil proteases human leukocyte elastase and cathepsin G, both in vitro and in vivo. Selectively O-desulfated heparin also inhibits complement lysis of erythrocytes, prevents ischemia-reperfusion injury of the lung, remains a potent antiproliferative treatment for cultured airway smooth muscle and normalizes altered neuronal M2 muscarinic receptor sensitivity and bronchial hyperreactivity after antigen challenge. These retained pharmacologic properties suggest possible use of this new nonanticoagulant heparin for the treatment of a variety of lung disorders.
 ...
PMID:Selective O-desulfation produces nonanticoagulant heparin that retains pharmacological activity in the lung. 922 56

Activation of cardiac muscarinic receptors by vagal stimulation decreases cardiac work, which may have a protective effect against ischemic injury. To determine whether cardiac muscarinic receptors contribute to the mechanisms of preconditioning effects, we examined the effect of carbachol on ischemia/reperfusion damage and the effect of vagotomy on cardioprotection induced by ischemic preconditioning. Rats were subjected to 30 min of left coronary artery occlusion followed by 30-min reperfusion in situ. Pre-conditioning was induced by three cycles of 2-min coronary artery occlusion and, subsequently by 5 min of reperfusion. The incidence of ischemic arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), and the development of myocardial infarction were markedly reduced by the preconditioning. Carbachol infusion (4 micrograms/kg per min) delayed the occurrence of VT and VF during ischemia and reduced the infarct size. Compared with non-ischemic left ventricle, the cyclic guanosine monophosphate (GMP) content in the ischemic region of the left ventricle was decreased by ischemia/reperfusion, whereas the cyclic adenosine monophosphate (AMP) content of this region was increased. These changes were reversed by preconditioning. Similar changes in cyclic GMP and AMP content in the ischemic region were seen in rats undergoing carbachol treatment. These results suggest the possible contribution of muscarinic receptor stimulation to preconditioning. Vagotomy prior to preconditioning diminished the antiarrhythmic effects, whereas it did not block the anti-infarct effect afforded by pre-conditioning. Vagotomy abolished the preconditioning effect on the tissue cyclic GMP, but it did not attenuate the decrease in tissue cyclic AMP. The results suggest that muscarinic stimulation exerts preconditioning-mimetic protective effects in ischemic/reperfused hearts, but that a contribution of reflective vagal activity to the mechanism for preconditioning is unlikely.
 ...
PMID:Activation of cardiac muscarinic receptor and ischemic preconditioning effects in in situ rat heart. 940 11

The control of arterial vascular tone by acetylcholine contributes to the regulation of cerebral blood flow. We analysed the effects of intraluminal application of acetylcholine (1microM) on the cerebral vascular tone by measuring changes in resistance to perfusion pressure in an isolated guinea-pig brain preparation maintained in vitro by arterial perfusion under constant flow. Acetylcholine induced a reproducible, fast-onset dilation that was prevented by the nitric oxide scavenger Methylene Blue (10microM) and by the muscarinic receptor antagonist atropine (0.1microM). Prolonged arterial perfusion with the nitric oxide synthase inhibitors N-nitro-L-arginine (1mM) and N-nitro-L-arginine methyl ester (30-100microM) induced a slowly developing increase of 25.9+/-13. 44mmHg in vascular tone and blocked the acetylcholine-induced vasodilation. In these experimental conditions, the dilation determined by the nitric oxide donor nitroprusside (0.1microM) was unaffected. In five experiments, the blockade of dilation unmasked a slow acetylcholine-mediated vasoconstriction (14.40+/-3.85mmHg) that was antagonized by atropine.The results demonstrate that acetylcholine exerts two simultaneous and opposite effects on guinea-pig cerebral vessels, characterized by a slow direct constriction concealed in physiological conditions by a fast vasodilation mediated through the release of nitric oxide by endothelial cells. Acetylcholine-mediated increase in vascular tone may play a role in aggravating cerebral perfusion when endothelial cell damage occurs during brain ischemia.
 ...
PMID:Nitric oxide synthase inhibitors unmask acetylcholine-mediated constriction of cerebral vessels in the in vitro isolated guinea-pig brain. 1107 51

Rhynchophylline and isorhynchophylline are major tetracyclic oxindole alkaloid components of Uncaira species, which have been long used as medicinal plants. In this study we examined the protective effects of rhynchophylline and isorhynchophylline on in vitro ischemia-induced neuronal damage in the hippocampus and interaction of these alkaloids with neurotransmitter receptors in a receptor expression model of Xenopus oocytes. In vitro ischemia was induced by exposing the hippocampal slices to oxygen- and D-glucose-deprived medium over 8 min. The resultant neuronal damage was elucidated as deterioration of population spike (PS) amplitudes evoked trans-synaptically by electrical stimulation of Schaffer collaterals and recorded in the CA1 area. Rhynchophylline and isorhynchophylline, as well as the N-methyl-D-aspartate (NMDA) antagonist (+/-)-2-amino-5-phosphono-valeric acid (APV), the muscarinic M1 receptor antagonist pirenzepine, and the 5-HT2 receptor antagonist ketanserin, attenuated the in vitro ischemia-induced neuronal damage in a concentration-dependent manner. There was no difference in the extent of protection against the neuronal damage between rhynchophylline and isorhynchophylline treatment. In Xenopus oocytes expressing the rat brain receptors encoded by total RNA, both rhynchophylline and isorhynchophylline reduced muscarinic receptor- and 5-HT2 receptor-mediated current responses in a competitive manner. Together with our previous findings that rhynchophylline and isorhynchophylline have a non-competitive antagonistic effect on the NMDA-type ionotropic glutamate receptors, the present results suggest that these alkaloids exert their protective action against ischemia-induced neuronal damage by preventing NMDA, muscarinic M1, and 5-HT2 receptors-mediated neurotoxicity during ischemia.
 ...
PMID:Protective effect of rhynchophylline and isorhynchophylline on in vitro ischemia-induced neuronal damage in the hippocampus: putative neurotransmitter receptors involved in their action. 1553 84

In this study, we investigated whether transient cerebral ischemia affects the function and molecular expression of specific muscarinic cholinergic receptors. Our results show that in contrast to the GABA-B and A1 adenosine receptor systems, the ability of muscarinic receptors to attenuate evoked excitatory responses at vulnerable CA1 synapses is significantly attenuated by 18 h following reperfusion. This attenuation in efficacy was restricted to the vulnerable CA1 subfield, as no significant change in muscarinic receptor-mediated attenuation of evoked responsiveness was observed within post-ischemic dentate granule cell synapses. Expression analysis revealed that the mRNA and immunoreactive protein levels for individual types of muscarinic receptors respond differently and uniquely to transient cerebral ischemia insult. Of particular interest is the m4 subtype of receptor, whose mRNA and protein expression levels were significantly diminished within the hippocampus by 12 and 24 h following reperfusion, respectively. As the m4 muscarinic receptor localizes to presynaptic terminals within the hippocampus, a decrease in its expression could account for the impaired functional responsiveness of the muscarinic receptor system following ischemic insult. Taken together, these results demonstrate that transient forebrain ischemia leads to dynamic alterations in the gene expression, protein prevalence, and functionality of muscarinic receptors in the post-ischemic hippocampus at times preceding the degeneration of the vulnerable neurons.
 ...
PMID:Decreased expression and impaired function of muscarinic acetylcholine receptors in the rat hippocampus following transient forebrain ischemia. 1595 Nov 92


<< Previous 1 2 3 4 Next >>