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

Endothelin-1 is a recently discovered peptide mainly released from endothelial cells. Hypoxia and ischemia as well as numerous factors such as angiotensin 11, thrombin and transforming growth factor beta 1 stimulate the formation of the peptide. On the other hand the synthesis of endothelin is inhibited by nitric oxide and atrial natriuretic peptide via the formation of cyclic guanosine monophosphate. Released from endothelial cells endothelin-1 mediates transient vasodilation followed by a profound and longlasting vasoconstriction. Endothelin is also a mitogen for smooth muscle proliferation. Endothelins exert their biological effects via activation of specific receptors. Two different receptors have been cloned from mammalian tissues (ET(A) and ET(B) receptors). On vascular smooth muscle cells both receptors mediate contractions. Endothelial cells only express ET(B) receptors linked to the formation of nitric oxide and/or prostacyclin formation. Increased plasma concentrations of endothelin-1 have been described in a variety of diseases such as pulmonary hypertension, arteriosclerosis, renal failure, acute coronary syndromes, heart failure, migraine and vascular diseases. Recently an increasing number of endothelin receptor antagonists have been synthetized, which have been shown to inhibit endothelin-mediated vasoconstriction. Clinical studies are now ongoing to elucidate the pathophysiologic role of endothelin and the potential benefit of the blockade of the system in different disease states.
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PMID:Endothelin and endothelin antagonists: potential role in cardiovascular and renal disease. 873 56

The normal functional state of the vasculature and the events leading to the development of significant arterial disease involve the interaction of important vasoactive substances, which play important modulating or initiating roles in the development of hypertension and arteriosclerosis. Three endothelins have now been identified, of which ET-1 is the best characterized. ET-1 is produced by epithelial, mesangial, neuronal and glial, and liver cells, and is the most potent vasoconstrictor yet found. Each endothelin is derived from a different gene on separate chromosomes, and each binds to at least 2 types of receptor. The plasma half-life of ET-1 is about 7 min, and this provides a rapid mechanism for adjusting vascular resistance or blood pressure. The actions of endothelin are mediated through several pathways of postreceptor signaling, including activation of the mitogen-activated protein kinase cascade, which give rise to its growth-stimulating properties. Secretion of ET-1 from cultured endothelial cells is stimulated by a wide range of substances, and is inhibited by some prostaglandins. Endothelin in turn stimulates secretion of nitric oxide, arginine vasopressin and atrial natriuretic peptide, and participates in the hormonal control of salt and water balance. Hypoxia and ischemia augment ET-1 secretion, as does insulin, and this could play a role in the accelerated vascular disease of diabetes. ET-1 also causes bronchoconstriction and has been implicated in the development of acute asthma, primary pulmonary hypertension and pulmonary fibrosis. Its role in hypertension is still debatable, though most of the manifestations of congestive heart failure can theoretically be explained by the actions of ET-1. Endothelin also has extensive renovascular and parenchymal effects in the kidney. It is hoped that a fuller understanding of the role of endothelins in normal or pathologic vasculature will lead to effective therapy based on antagonism or augmentation of specific functions.
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PMID:Endothelins as cardiovascular peptides. 873 84

Coronary angioplasty has been the favoured model in studying ischemic preconditioning in humans, but results have remained controversial, possibly due to some artefacts related to coronary balloon angioplasty as an ischemia model. We examined this issue by monitoring the sequential metabolic, functional and neurohumoral changes during repeated vessel occlusion in coronary angioplasty performed in patients with chronic angina pectoris. Two groups of patients undergoing two successive balloon inflations of approximately 2 min duration were studied. These balloon inflations were preceded by a short inflation performed immediately after introduction of the balloon into the stenosis. The aim of this primary inflation was to establish adequate coronary blood flow with the deflated balloon in the stenosis and to guarantee that the subsequent two balloon inflations were truly comparable in time. Group I consisted of 23 patients, in whom the changes in the degree of angina, pulmonary capillary wedge pressure (PCWP), atrial natriuretic peptide (ANP) and circulating catecholamines during the procedure were studied. The sequential changes in myocardial metabolism were monitored in group II of nine patients by determining the lactate extraction ratios and femoroarterial coronary sinus (Fa-CS) differences in pH and pCO2 before and after each balloon inflation. In group I, PCWP and total catecholamines increased similarly during both balloon inflations, but ANP remained unchanged. In group II patients the lactate extraction ratios turned negative, the Fa-CS pH-differences increased and the pCO2-differences decreased during vessel occlusions, the changes being somewhat more prominent during the second balloon inflation. To study adaptation to ischemia, the group I patients were divided into two subgroups with and without signs of ischemic dysfunction during balloon inflations (PCWP increase > 5 mmHg and < 5 mmHg, respectively), and the group II patients were divided into two subgroups with and without metabolic ischemia (lactate-producers and non-producers). The ANP levels were constantly higher in the patients demonstrating ischemic dysfunction during balloon inflations, but catecholamine levels increased only after the second balloon inflation. The anginal pain experienced by the patients and the signs of metabolic ischemia were identical during both balloon inflations. We conclude that acute ischemic preconditioning does not occur in patients with repeated vessel occlusions of approximately 2 min duration. The patients without ischemia during the procedure had more critical stenoses and pre-existing collaterals. However, other protective mechanisms, such as chronic adaptation at the cellular level or recruitment of new collaterals, cannot be excluded.
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PMID:No evidence for ischemic preconditioning during repeated vessel occlusion in coronary angioplasty. 887 22

Polymorphonuclear leukocytes (PMN), atrial natriuretic peptide (ANP) and leukotriene B4 (LTB4) reportedly play a major role in ischemia/reperfusion states of coronary artery disease. We sought to determine whether ANP and LTB4 cooperate in inducing PMN activation with consequent modulation of membrane molecules required for adherence to endothelium and myocardial cells, namely CD11b and L-selectin and the release of toxic oxygen radicals. ANP (from 10(-16) to 10(-8) M), LTB4 (from 10(-10) to 10(-6) M) and combinations of the two were incubated with normal PMN at 37 degrees C for 15 minutes. Membrane molecules modulation was measured by flow cytometry using specific monoclonal antibodies. Hydrogen peroxide production, an indicator of the capacity of PMN to release toxic oxygen species was quantified by flow cytometry using the peroxide-sensitive fluorescent probe dichlorofluorescein diacetate. ANP, uneffective when used alone, dose-dependently potentiated the PMN response to LTB4 (10(-9) M) as evidenced by an up-regulation of CD11b expression and peroxide production, and a down-regulation of L-selectin expression. These effects were prevented dose-dependently by the protein kinase C (PKC) inhibitor staurosporine (from 10 to 160 microM). Two carnitine congeners, palmytoylcarnitine (tested from 125 pg to 2 micrograms/ml) that also possesses an established ability to antagonise PKC and L-carnitine (tested from 12 to 200 ng/ml) were also effective. These data indicate that ANP potentiates LTB4 in inducing PMN mobilization and activation with a possible consequent detrimental effect on cardiac tissue and evisages the usefulness of PMN metabolism modulators.
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PMID:Potentiation of human polymorphonuclear leukocyte activation by atrial natriuretic peptide. Inhibitory effect of carnitine congeners. 892 47

Contralateral uninephrectomy attenuates unilateral ischemic injury. The present work was performed to elucidate whether the beneficial effect of uninephrectomy was associated with the modification of ischemia-induced changes in plasma or renal renin activity. A 60-min left renal artery occlusion was conducted in right nephrectomized (Nx) and sham-nephrectomized (Sham-Nx) rats. The decline in inulin clearance 48 h after ischemia was significantly less in Nx rats than in Sham-Nx animals (0.50 +/- 0.10 vs. 0.052 +/- 0.029 ml/min/kidney, p < 0.05). Following ischemia, plasma renin activity (PRA) significantly increased in Sham-Nx (from 5.4 +/- 0.9 to 15.5 +/- 1.4 ng AI/ml/min, p < 0.01) but not in Nx (from 3.5 +/- 0.5 to 5.0 +/- 1.0 ng AI/ml/ min) animals. PRA and renal cortical renin content (2,200 +/- 225 vs. 1,257 +/- 187 ng AI/h/mg protein, p < 0.05) were significantly less in Nx rats than in Sham-Nx animals 48 h after renal ischemia. The decrease in body weight was greater in Nx rats than in Sham-Nx animals. Plasma atrial natriuretic peptide (ANP) (195 +/- 30 vs. 302 +/- 40 pg/ml, p < 0.05) and renal dopamine (DA) content (3.2 +/- 0.5 vs. 13.7 +/- 1.3 ng/g tissue, p < 0.01) were rather lower in the Nx group when compared with the Sham-Nx group. No significant difference was found in the intrarenal content of norepinephrine (NE) between two ischemic groups. These findings suggested that uninephrectomy prevents the ischemia-induced increase in renin activity. The prevention of the increase in renin activity in Nx rats is not be mediated through the modulation of ischemia-induced changes in sodium balance, plasma ANP level and/or intrarenal contents of NE and DA.
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PMID:Uninephrectomy prevents the ischemia-induced increase in renin activity. 903 Dec 73

Angiotensin-converting enzyme inhibitors (ACEi) protect the heart against ischemia/reperfusion injury. Part of this cardioprotective effect may be mediated through kinins. Because kinins are also metabolized by neutral endopeptidase (NEP) 24.11 in vivo, we hypothesized that (a) inhibition of NEP-24.11 would afford cardioprotection similar to that of ACEi and potentiate the effect of ACEi; and (b) these effects are mediated by kinins or atrial natriuretic peptide (ANP) or both. In Lewis inbred rats, the left anterior descending coronary artery (LAD) was occluded for 30 min, followed by 120-min reperfusion. Immediately before reperfusion rats received vehicle, the ACEi ramiprilat, the NEP-24.11 inhibitor (NEPi) CGS24592, or both. To test whether the effect of NEPi could be suppressed by blocking kinins or ANP, the kinin-receptor antagonist icatibant or ANP antagonist HS-142-1 was administered before LAD occlusion. In controls, infarct size/risk area was 69 +/- 4%; NEPi reduced this to 24 +/- 4% (p < 0.001) and ramiprilat to 20 +/- 3% (P < 0.001). NEPi did not potentiate the effect of ramiprilat (infarct size/risk area, 18 +/- 4%). The protective effect of NEPi was blocked by icatibant; infarct size/risk area, 61 +/-4%, significantly larger than NEPi along (p < 0.001) but no different from controls. The effect of NEPi was slightly diminished by the ANP antagonist HS-142-1 (infarct size/risk area, 35 +/- 3%; NS vs. NEPi alone). Thus NEP-24.11 participates in catabolism of kinins in the heart; inhibition of NEP-24.11 may increases cardiac kinins, which are responsible for the cardioprotective effect of NEPi.
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PMID:Effect of neutral endopeptidase 24.11 inhibition on myocardial ischemia/reperfusion injury: the role of kinins. 905 75

The effect of intraventricular atrial natriuretic peptide (ANP) on elevated intracranial pressure (ICP) was evaluated in a rodent model of global ischemia and reperfusion. ANP administration into the lateral ventricle 30 minutes after reperfusion statistically significantly reduced ICP compared with both vehicle treated animals (p < 0.001) and pretreatment pressures (p < 0.001). The ICP effects of ANP did not coincide with specific changes in regional perfusion parameters measured by laser-Doppler flowmetry. Two different vehicles for ANP were used to verify that the changes in ICP observed were independent of the sodium content administered in the vehicle. Based on the reductions observed in ICP, ANP deserves further evaluation as a treatment modality for the acute elevations in ICP associated with ischemic brain injury.
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PMID:Intraventricular atrial natriuretic peptide for acute intracranial hypertension. 932 29

The aim of our studies was to investigate hormonal prevention of hepatic preservation damage by the atrial natriuretic peptide (ANP) and the mechanisms involved. Isolated perfusion of rat livers was performed in a nonrecirculating fashion. Twenty minutes of preischemic perfusion was performed with or without different concentrations of ANP, followed by 24-hour storage in cold University of Wisconsin (UW) solution. Two hundred nanomoles of ANP prevented hepatocellular damage during a 2-hour reperfusion period as indicated by a marked attenuation of the sinusoidal efflux of lactate dehydrogenase (LDH) and purine nucleoside phosphorylase (PNP), and by reduced Trypan blue uptake. Furthermore, postischemic bile flow as an indicator of liver function was significantly improved by about 60% with 200 nmol/L ANP. No protection was conveyed by 20 nmol/L ANP nor by pretreatment with 200 nmol/L ANP for only 10 minutes. The effects of ANP seemed to be mediated by the guanylate cyclase-coupled A (GC-A) receptor and cyclic guanosine monophosphate (cGMP): whereas expression of both GC-A and GC-B receptors as well as of the GC-C receptor was found, cGMP did protect from ischemia-reperfusion damage, but selective ligands of the B and C receptor did not. To begin to determine the mechanisms of ANP-mediated protection, different parameters were investigated: ANP had no effect on portal pressure as an indicator of hepatic circulation, nor on intracellular energy depletion determined by adenosine nucleotide concentration. However, the marked augmentation of nuclear factor kappaB (NF-kappaB) binding activity during reperfusion was prevented in ANP-pretreated livers. In conclusion, pretreatment with ANP protects the rat liver from cold ischemia-reperfusion damage. This effect is mediated via the GC-A receptor and cGMP, and may be linked to an influence of ANP on NF-kappaB activation. Thus, ANP signaling via the GC-A receptor should be considered as a new pharmacological target to prevent preservation injury of the liver.
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PMID:The guanylate cyclase-coupled natriuretic peptide receptor: a new target for prevention of cold ischemia-reperfusion damage of the rat liver. 979 16

-Previous studies suggested that atrial natriuretic peptide gene (Anp) and brain natriuretic peptide gene (Bnp) are plausible candidate genes for susceptibility to stroke and for sensitivity to brain ischemia in the stroke-prone spontaneously hypertensive rat (SHRSP). We performed structural and functional analyses of these 2 genes in SHRSP from Glasgow colonies (SHRSPGla) and Wistar-Kyoto rats from Glasgow colonies (WKYGla) and developed a radiation hybrid map of the relevant region of rat chromosome 5. Sequencing of the coding regions of the Anp and Bnp genes revealed no difference between the 2 strains. Expression studies in brain tissue showed no differences at baseline and at 24 hours after middle cerebral artery occlusion. Plasma concentrations of atrial natriuretic peptide (ANP) did not differ between the SHRSPGla and WKYGla, whereas concentrations of brain natriuretic peptide were significantly higher in the SHRSPGla as compared with the WKYGla (n=11 to 14; 163+/-21 pg/mL and 78+/-14 pg/mL; 95% confidence interval 31 to 138, P=0.003). We did not detect any attenuation of endothelium-dependent relaxations to bradykinin or ANP in middle cerebral arteries from the SHRSPGla; indeed the sensitivity to ANP was significantly increased in arteries harvested from this strain (WKYGla: n=8; pD2=7. 3+/-0.2 and SHRSPGla: n=8; pD2=8.2+/-0.15; P<0.01). Moreover, radiation hybrid mapping and fluorescence in situ hybridization allowed us to map the Anf marker in the telomeric position of rat chromosome 5 in close proximity to D5Rat48, D5Rat47, D5Mgh15, and D5Mgh16. These results exclude Anp and Bnp as candidate genes for the sensitivity to brain ischemia and pave the way to further congenic and physical mapping strategies.
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PMID:Genes encoding atrial and brain natriuretic peptides as candidates for sensitivity to brain ischemia in stroke-prone hypertensive rats. 993 Nov 19

Long-term angiotensin-converting enzyme (ACE) inhibition may reduce ischemic events in patients with coronary artery disease, but whether it protects against acute ischemia or the effects of preexisting left ventricular (LV) dysfunction on potential anti-ischemic properties is unknown. We performed a double-blind trial in 25 patients with exercise-induced ischemia. The effects of perindoprilat on pacing-induced myocardial ischemia were examined. Fourteen patients received perindoprilat and 11 patients received placebo. Based on LV function, 2 subgroups were formed in the perindoprilat group: 7 patients with LV dysfunction (LV ejection fraction <0.40), and 7 patients with normal LV function. After receiving the study medication, the pacing test was repeated. During the first pacing test both groups developed ischemia. After perindoprilat administration, the increase in systemic vascular resistance and LV end-diastolic pressure were significantly blunted (p <0.05). Further, the ischemia-induced increase in arterial and cardiac uptake of norepinephrine was inhibited by perindoprilat, and the increase in atrial natriuretic peptide was less pronounced; also, ST-segment depression was reduced by 32% compared with placebo (all p <0.05). In the group with LV dysfunction, perindoprilat reduced LV end-diastolic pressure significantly by 67% and myocardial lactate production was prevented, but this did not happen in the group with normal LV function. In addition, the increase in arterial norepinephrine was reduced by 74% and 33%, respectively (p <0.05). These results indicate that perindoprilat reduced acute, pacing-induced ischemia in normotensive patients. In patients with (asymptomatic) LV dysfunction these effects were more pronounced than in patients with normal LV function.
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PMID:Acute anti-ischemic effects of perindoprilat in men with coronary artery disease and their relation with left ventricular function. 1007 18


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