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

Pre-eclampsia or pregnancy induced hypertension (PIH) affects 6-8% of all pregnancies. Although the underlying mechanism of PIH is still unknown, it is widely believed that the placenta plays an important role. It was thought that an ischemic placenta due to poor perfusion can precipitate the signs and symptoms of PIH. This study aims to investigate the possible role of Type 1(AT1) and Type 2 (AT2) angiotensin II receptor subtypes in the mechanism of PIH. AT1 receptor stimulation causes vasoconstriction and AT2 receptor stimulation causes vasodilatation. Investigating the interactions of these two receptors in the placenta provides an insight as to the balance that may exist between AT1 and AT2 receptors in normal pregnancy. Any disruption to the balance might cause a disruption of the blood flow in the placenta, leading to PIH. Placentas were collected from 11 PIH patients and 11 normal patients. Immunohistochemistry techniques were performed on the placental tissue to determine the distribution of AT1 and AT2 receptors in the placental tissue qualitatively and quantitatively. It was observed that in normal patients, the balance between AT1 and AT2 receptors is that the level of AT2 receptors is higher than the level of AT1 receptors. However in the PIH patient, it was observed that the normal balance was disrupted. In PIH patients the level of AT1 receptors was observed to be higher than the level of AT2 receptors. This study suggests that disruption of the balance between AT1 and AT2 receptors observed in PIH placentas might cause a decrease in blood flow to the placenta, causing it to be poorly perfused. This may cause placental ischemia which may lead to PIH.
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PMID:A preliminary finding: immunohistochemical localisation and distribution of placental angiotensin II receptor subtypes in normal and preeclamptic pregnancies. 1689 8

Among the general heart failure (HF) population, over half have diastolic HF (DHF). The proportion of DHF increases with age, from 46% in patients younger than 45 years to 59% in patients older than 85 years. The diagnosis of DHF is made by the combination of signs and symptoms of HF with preserved systolic function (left ventricular ejection fraction >50%), and evidence of diastolic dysfunction obtained by echocardiographic Doppler examination, invasive hemodynamic evaluation, or an elevation of serum B-type natriuretic peptide. The most common risk factors for the development of diastolic dysfunction and DHF include long-standing hypertension, older age, female sex, obesity, diabetes, chronic kidney disease, and coronary artery disease. Acute decompensation occurs in the setting of pressure overload, volume overload, or superimposed cardiac ischemia. The cornerstones of in-hospital management include blood pressure and volume control, heart rate control, and correction of precipitating factors. Priorities in the outpatient clinic include optimal blood pressure control, maintenance of euvolemia with minimal or no diuretics, and, potentially, use of disease-modifying drugs including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, aldosterone receptor blockers, beta-blockers, and digoxin. Long-term regression of left ventricular hypertrophy, improvement in diastolic filling parameters, and sustained reductions in B-type natriuretic peptide may be future treatment targets for this condition.
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PMID:Curriculum in cardiology: integrated diagnosis and management of diastolic heart failure. 1758 43

Previous studies have indicated that nitric oxide synthase (NOS) inhibitors can induce an increase of blood pressure and exacerbate myocardial injury induced by ischemia and reperfusion, whereas angiotensin II receptor antagonists protect the myocardium against injury induced by ischemia and reperfusion. Isolated hearts from male spontaneously hypertensive rats (SHR) or male Wistar-Kyoto rats (WKY) were subjected to 20 min global ischemia and 30 min reperfusion. Heart rate, coronary flow, left ventricular pressure, and its first derivatives (+/-dP/dt(max)) were recorded, and serum concentrations of asymmetric dimethylarginine (ADMA) and NO and the release of creatine kinase in coronary effluent were measured. The level of ADMA was significantly increased and the concentration of NO was decreased in SHR. Ischemia and reperfusion significantly inhibited the recovery of cardiac function and increased the release of creatine kinase, and ischemia and reperfusion-induced myocardial injury in SHR was aggravated compared with WKY. Vasodilation responses to acetylcholine of aortic rings were decreased in SHR. Treatment with losartan (30 mg/kg) for 14 days significantly lowered blood pressure, elevated the plasma level of NO, and decreased the plasma concentration of ADMA in SHR. Treatment with losartan significantly improved endothelium-dependent relaxation and cardiac function during ischemia and reperfusion in SHR. Exogenous ADMA also aggravated myocardial injury induced by ischemia and reperfusion in isolated perfused heart of WKY, as shown by increasing creatine kinase release and decreasing cardiac function. The present results suggest that the protective effect of losartan on myocardial injury induced by ischemia and reperfusion is related to the reduction of ADMA levels.
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PMID:Reduction of asymmetric dimethylarginine involved in the cardioprotective effect of losartan in spontaneously hypertensive rats. 1790 88

Because no controlled clinical studies are available about the possible role of angiotensin II receptor blockers in preventing effort myocardial ischemia, we evaluated the effect of angiotensin II receptor blocker/losartan in preventing exercise-induced myocardial ischemia in patients with coronary artery disease. Twenty-four sedentary patients with chronic stable ischemia were prospectively randomized to 28 days (double blind) of losartan 100 mg or losartan placebo in 2 divided doses. In each patient the treatment was crossed over to the alternative regimen (28 days, double blind) after a 1-week placebo period (single blind). At the end of each phase a new exercise stress test was performed. At baseline, systolic blood pressure was significantly decreased after losartan 100 mg compared with losartan placebo. At submaximal exercise, systolic blood pressure and rate-pressure product were lower after losartan 100 mg administration compared with losartan placebo, and these findings remained significant at 1-mm ST depression and at peak exercise. Losartan 100 mg administration versus losartan placebo significantly delayed the time to 1-mm ST-depression onset and decreased ST-segment depression at peak exercise and time to recovery of ST-segment depression. Losartan 100 mg administration compared with losartan placebo was able to significantly increase exercise duration and maximal workload during exercise stress testing. In conclusion, in our study, losartan decreased electrocardiographic parameters of myocardial ischemia in patients with coronary artery disease, suggesting a possible role of this drug in treatment of patients with effort myocardial ischemia.
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PMID:Effect of losartan in treatment of exercise-induced myocardial ischemia. 1799 11

Oxidative stress (OS) is a keystone in the pathology of the ischemia reperfusion sequence (acute coronary syndromes, cardiac surgery, transplantation). In heart failure, the implication of OS is less understood. This study was intended to evaluate OS in acute heart failure. Criteria for inclusion were consecutive patients hospitalized in our cardiology department for a first pulmonary edema that revealed a dilated cardiomyopathy (DCM). Exclusion criteria included known cardiomyopathy, smoker, acute coronary syndrome, and treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARAII). OS was evaluated in blood samples: thiobarbituric acid-reactive substances (TBARS), total antioxidant status (TAS), plasma alpha-tocopherol, vitamin A, and beta-carotene. Standard biochemical parameters including CRP, fibrinogen, lipid, and creatinine were assayed. Ten patients (80% men, mean age 55.3 +/- 7.9 years) were included and followed during a 6 month period. The etiologies of DCM were alcohol (n = 3), anti-cancer drugs (n = 2), valvulopathies (n = 2), or idiopathic (n = 3). In acute heart failure, TBARS were elevated (1.69 micromol/L; normal value 0.6-4.2 micromol/L) and TAS status was decreased (0.96 mmol/L; normal value 1.3-1.9 pmol/L). OS was more important when patients had atrial or ventricular arrhythmia. Nevertheless, liposoluble antioxidant parameters (beta-carotene, vitamin A, alpha-tocopherol) had a usual value. At the term of the follow-up, patients returned to a stable condition, OS markers revealed normal values, and every Holter ECG showed no supraventricular or ventricular arrhythmias. In acute heart failure, oxygen-free radicals are increased. We thus hypothetized that a modification in OS could be responsible for arrhythmias and complications of acute heart failure.
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PMID:Oxidative stress in patients with acute heart failure. 1839 53

Azelnidipine has been reported to have antioxidant effects and attenuates tubulointerstitial ischemia. The aim of the present study was to determine whether azelnidipine exerts additional renoprotective effects to angiotensin II receptor blockers (ARBs) in hypertensive patients with diabetic nephropathy and microalbuminuria. 45 hypertensive patients with diabetes mellitus and microalbuminuria who were already being treated with ARBs were enrolled in this study. Azelnidipine was added to the drug treatment of 30 patients (8 mg/day, n = 15, or 16 mg/day, n = 15) whilst the remaining 15 control patients were not treated with azelnidipine. In all patients, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and urinary liver-type fatty acid-binding protein (L-FABP) levels were significantly correlated (r = 0.587, p = 0.0006). However, urinary albumin excretion (UAE) was not correlated with the levels of urinary 8-OHdG (r = 0.1975, p = 0.2956) or urinary L-FABP (r = 0.2057, p = 0.2759). Azelnidipine significantly reduced UAE, urinary 8-OHdG and urinary L-FABP after 6 (p < 0.05) and 12 months (p < 0.05). Although blood pressure was comparable between the azelnidipine doses of 8 and 16 mg/day, the UAE (p < 0.05 after 12 months), urinary 8-OHdG (p < 0.05 after 6 and 12 months) and urinary L-FABP (p < 0.05 after 6 and 12 months) levels were more significantly reduced in patients receiving the higher dose of 16 mg/day. These data may suggest that the addition of azelnidipine treatment to therapy with ARBs has dose-dependent antioxidant and renoprotective effects beyond blood pressure-lowering effects in hypertensive diabetic nephropathy patients.
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PMID:Additional renoprotective effects of azelnidipine combined with angiotensin receptor blockers in patients with diabetic nephropathy. 1900 May 38

Normal pregnancy is associated with significant hemodynamic changes and vasodilation in the uterine and systemic circulation in order to meet the metabolic demands of the mother and developing fetus. Hypertension in pregnancy (HTN-Preg) and preeclampsia (PE) are major complications and life-threatening conditions to both the mother and fetus. PE is precipitated by various genetic, dietary and environmental factors. Although the initiating events of PE are unclear, inadequate invasion of cytotrophoblasts into the uterine artery is thought to reduce uteroplacental perfusion pressure and lead to placental ischemia/hypoxia. Placental hypoxia induces the release of biologically active factors such as growth factor inhibitors, anti-angiogenic proteins, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and antibodies to vascular angiotensin II receptor. These bioactive factors affect the production/activity of various vascular mediators in the endothelium, smooth muscle and extracellular matrix, leading to severe vasoconstriction and HTN. As an endothelial cell disorder, PE is associated with decreased vasodilator mediators such as nitric oxide, prostacyclin and hyperpolarizing factor and increased vasoconstrictor mediators such as endothelin, angiotensin II and thromboxane A(2). PE also involves enhanced mechanisms of vascular smooth muscle contraction including intracellular free Ca(2+) concentration ([Ca(2+)](i)), and [Ca(2+)](i) sensitization pathways such as protein kinase C, Rho-kinase and mitogen-activated protein kinase. Changes in extracellular matrix composition and matrix metalloproteases activity also promote vascular remodeling and further vasoconstriction in the uterine and systemic circulation. Characterization of the predisposing risk factors, the biologically active factors, and the vascular mediators associated with PE holds the promise for early detection, and should help design specific genetic and pharmacological tools for the management of the vascular dysfunction associated with HTN-Preg.
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PMID:Risk factors and mediators of the vascular dysfunction associated with hypertension in pregnancy. 2004 38

We investigated the protective effect of telmisartan, an angiotensin II receptor antagonist, against ischemia/reperfusion renal injury in rats. Bilateral ischemia was induced by clamping both renal vascular pedicles for 45 min followed by reperfusion for 3 h. Untreated rats exposed to ischemia/reperfusion showed significant elevations in blood urea nitrogen and serum creatinine levels, renal tissue levels of malondialdehyde, tumor necrosis factor-alpha and nitric oxide, and caspase-3 activity. This was associated with significant decreases in renal reduced glutathione level, catalase and superoxide dismutase activities. Also, significant increases in serum and renal tissue levels of homocysteine were detected following ischemia/reperfusion. Pre-ischemic treatment with telmisartan (0.3 mg/kg/day, i.p.) for 7 consecutive days significantly attenuated the increases in blood urea nitrogen, serum creatinine, renal malondialdehyde, tumor necrosis factor-alpha, nitric oxide, caspase-3 activity, and serum and renal homocysteine levels, and significantly restored the renal antioxidant defenses. In addition, light and electron microscopic examinations revealed that telmisartan pre-treatment markedly ameliorated ischemia/reperfusion-induced renal tissue damage. It was concluded that telmisartan, through its antioxidant, anti-inflammatory and antiapoptotic effects, can be considered a potential candidate to protect against acute ischemia/reperfusion renal injury.
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PMID:Nephroprotective effect of telmisartan in rats with ischemia/reperfusion renal injury. 2015 Jul 54

Reactive oxygen species are known to be derived from NADPH oxidase in several tissues. Angiotensin II was suggested to be involved in the activation of NADPH oxidase; however, its role in the gastric mucosa is unclear. We examined the roles of angiotensin II receptor and NADPH oxidase in ischemia/reperfusion-induced gastric damage in rats. Under urethane anesthesia, male Sprague-Dawley rat stomachs were mounted in an ex-vivo chamber, had 100 mM HCl applied to them, and then a catheter was passed through the femoral vein. Ischemia/reperfusion was accompanied by blood collection and reperfusion through the catheter. Losartan, candesartan, valsartan, which are AT1 receptor blockers (ARB); PD123319, an AT2 receptor blocker; enalapril, an ACE inhibitor; or diphenylene iodonium, a NADPH oxidase inhibitor, was given i.v. 10 mins, and beta-NADPH, a NADPH oxidase substrate, was given i.v. 5 mins before reperfusion. The gastric damage by ischemia/reperfusion was attenuated by treatment with any of ARB or enalapril, but was not affected by PD123319. The increase in gastric H(2)O(2) production and microvascular permeability by ischemia/reperfusion was also suppressed by treatment with any of ARB or enalapril. In rat gastric mucosa, the NADPH oxidase subunit p47(phox) was detected. Additionally, diphenylene iodonium had similar effects to ARB against ischemia/reperfusion-caused gastric damage, increased H(2)O(2) production, and microvascular permeability. Ischemia/reperfusion activated NADPH oxidase in the gastric mucosa, and the activation was significantly attenuated by treatment with losartan or diphenylene iodonium. These results suggest that ischemia/reperfusion generated reactive oxygen species are derived from NADPH oxidase activation via AT1 receptor in rat stomachs.
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PMID:Evidence for the involvement of NADPH oxidase in ischemia/reperfusion-induced gastric damage via angiotensin II. 2043 17

The present study was designed to test pretreatment multiple doses of irbesartan (IRB) 50 mg, aspirin (ASP) 100 mg and the combination of both drugs for 7 days on middle cerebral artery-occluded (MCAO) rats. Focal cerebral ischemia was induced by MCA occlusion for 2 hours followed by reperfusion for 22 hours. After 24 hours of ischemia, grip strength and locomotor activity tests were performed. Animals were immediately sacrificed, infarct volume was measured followed by the estimation of markers of oxidative stress in the whole brains. Locomotor activity and grip strength were improved in IRB- and ASP-treated rats. Infarct volume was reduced in both IRB and ASP pretreatment as compared with MCAO rats. An elevation of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione (GSH) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase were observed following MCAO. Pretreatment of IRB and ASP showed the reduction in TBARS, elevation in GSH, SOD and catalase levels as compared with MCAO rats. The protective effects of IRB, an angiotensin II receptor antagonist having affinity for AT(1) receptor subtypes, could be due to inhibition of AT( 1) receptor expression in addition to its neuroprotective and free radical scavenging properties in cerebral ischemia. Further, it may be possible that the combination of IRB and ASP may be useful as an add-on therapy and would yield beneficial effects, if administered immediately following the ischemia in reducing the severity of the neurological deficits. However, our results are preliminary, further studies with posttreatment of IRB and ASP are required to provide more firm view.
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PMID:Protective effect of irbesartan, an angiotensin II receptor antagonist, alone and in combination with aspirin on middle cerebral artery occlusion model of focal cerebral ischemia in rats. 2048 39


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