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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the changes in pulmonary hemodynamics and lung wet weight induced with opsonized zymosan (OZ) in isolated guinea pig lungs perfused with Ringer-albumin solution containing neutrophils (PMNs). Addition of OZ to the PMN-perfused lungs caused pulmonary vasoconstriction and weight gain; neither OZ nor PMNs added individually to the perfusate altered pulmonary vasomotor tone or wet weight. The steady gain in lung weight by 1,588 +/- 464 mg over the 45-minute study period was associated with pulmonary capillary hypertension and an increase in the capillary filtration coefficient, indicative of increased lung vascular permeability. These responses may not be due to generation of oxygen radicals, because the alterations in pulmonary hemodynamics and lung weight were not reduced by addition of superoxide dismutase, catalase, or superoxide dismutase plus catalase. We examined the basis of the PMN-mediated effects by layering PMNs on bovine pulmonary artery endothelial monolayers. Challenge with OZ resulted in increased endothelial permeability to 125I-albumin. The monoclonal antibody IB4 (directed against CD18, the common beta-subunit of structurally related adhesion receptors on phagocytes, LFA-1, Mac-1, and P150,95) prevented the OZ-mediated increase in PMN adherence to endothelial cells and the increase in endothelial permeability to 125I-albumin. IB4 also inhibited the lung weight gain mediated by the OZ-stimulated PMNs in intact lungs. The protective effect of IB4 could be ascribed neither to inhibition of uptake of OZ by PMNs nor to inhibition of release of oxygen radicals, myeloperoxidase, and elastase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary edema induced by phagocytosing neutrophils. Protective effect of monoclonal antibody against phagocyte CD18 integrin. 197 52

The biochemical mechanisms by which hypertension accelerates atherosclerosis and increases the risk of aortic aneurysm rupture are poorly understood. This study evaluates the effects of hypertension on aortic trace element concentrations and antioxidant status in tissue removed from 26 normotensive (NT) and 20 hypertensive (HT) patients. Twenty-seven of 46 patients (59%) had aneurysmal (AA), and 19 of 46 (41%) had occlusive disease (OD). Aortic iron concentrations were markedly higher in both OD and AA tissue compared with controls. A similar trend was observed with copper concentrations, with the highest elevations observed in HT AA tissues. No significant differences were observed in zinc concentrations, except that HT AA aorta had significantly lower zinc levels than either OD or control tissue. Aortic ascorbic acid concentrations in diseased aorta were lower than those of controls, but independent of blood pressure. Copper-zinc-superoxide dismutase activity was similarly reduced, with the lowest activity observed in diseased aorta from HT patients. Only HT AA aorta had significantly higher manganese-superoxide dismutase activity than controls. The aortas of patients with AA had significantly lower amounts of elastin and greater elastase activity than either controls or those with OD. However, the differences were independent of blood pressure. Hypertensive patients with OD and AA had 31% more and 27% less aortic collagen, respectively, than their NT counterparts (P less than 0.05). These data suggest that the reduction in aortic collagen and elastin in HT patients with AA compared with their NT counterparts may explain the larger size of aneurysms and predispose to their eventual rupture. Furthermore, the diminished antioxidant status associated with HT predisposes to lipid peroxidation, which contributes to the acceleration of these processes. Our studies were conducted in patients with established aortic aneurysmal and occlusive disease. Whether these observations are pertinent to the pathogenesis of AA and OD remains unclear and merits further study.
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PMID:Effects of hypertension on aortic antioxidant status in human abdominal aneurysmal and occlusive disease. 199 4

Oxygen radicals are known to be produced by the cerebral vasculature during acute, pressor-induced hypertension and are also known to inactivate endothelium-derived relaxing factor. The objective of our present study was to determine if the oxygen radical scavenger superoxide dismutase (24,000 units/kg plus 1,600 units/kg/min) alters the pressor, cerebral blood flow, and mortality responses to systemic norepinephrine in rats. Increasing doses (0.01-30 micrograms/kg i.v.) of norepinephrine were given by bolus injection to eight rats, and changes in the cortical microcirculatory blood flow were measured by laser-Doppler flowmetry. Superoxide dismutase shifted the norepinephrine-blood pressure and -cerebral blood flow dose-response curves moderately, but significantly, to the right such that it took more norepinephrine to reach a given blood pressure. However, superoxide dismutase had no effect on the autoregulation of cerebral blood flow. Additionally, whereas five (63%) of the eight control rats died after the 10 micrograms/kg norepinephrine dose, all eight rats treated with superoxide dismutase survived this dose. The mechanism by which superoxide dismutase reduced mortality is uncertain. The blood pressure and cerebral blood flow results suggest that superoxide dismutase prevents oxygen radicals from destroying endothelium-derived relaxing factors, which reduce the pressor effects of norepinephrine.
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PMID:Superoxide dismutase decreases mortality, blood pressure, and cerebral blood flow responses induced by acute hypertension in rats. 202 78

The Dahl salt-sensitive rat was used to investigate the effect of hypertension on indexes of copper status and to determine the extent to which dietary manipulation of copper attenuated, or exacerbated, the rate of sodium chloride-induced hypertension. Weanling salt-sensitive rats were fed, in a 2 x 3 factorial design, one of six diets that contained one of three levels of copper (2.0 micrograms/g marginal, 12 micrograms/g adequate, or 50 micrograms/g supplemental) and either control (0.4%) or high (4%) levels of sodium. Diets were fed to the rats for 11 weeks. Rats fed the high sodium diets were characterized by high plasma copper concentrations and ceruloplasmin activities compared with their respective control sodium rats. The magnitude of the sodium-induced rise in plasma copper and ceruloplasmin was affected by dietary copper intake; however, dietary copper intake had no effect on the development of hypertension in the high sodium groups. These results suggest that altered copper metabolism is secondary, rather than primary, to the development of sodium chloride-induced hypertension in the salt-sensitive rat. Red blood cell superoxide dismutase activity was reduced in rats fed the low copper diets compared with the adequate and supplemented copper groups. At the lower levels of copper intake, sodium chloride-induced hypertension increased red blood cell superoxide dismutase activity in a manner consistent with the plasma copper and ceruloplasmin changes observed. However, at adequate or supplemental levels of dietary copper, red blood cell superoxide dismutase activity plateaued, suggesting possible saturation of copper at sites of hematopoeisis.
Hypertension 1991 Jun
PMID:Influence of hypertension and dietary copper on indexes of copper status in rats. 204 41

The great discovery by Furchgott of the relaxing factor released from the endothelium (EDRF) awakened us to the necessity to reevaluate the functional importance of endothelial cells that have been chemically or physically stimulated. EDRF was first demonstrated to be released by acetylcholine, substance P, bradykinin and calcium ionophore A23187; thereafter, many substances have been found to release EDRF. This factor is quite unstable, is not produced by cyclooxygenase, and is an activator of soluble guanylate cyclase that synthesizes cyclic GMP; its action is suppressed by antioxidants via the superoxide anions produced, potentiated by superoxide dismutase and abolished by methylene blue and oxyhemoglobin. Recently, the role of lipoxygenase products in the production of EDRF was evaluated with new 5-lipoxygenase inhibitors without antioxidant activity. During the last couple of years, the actions and chemical properties of EDRF were verified to be quite similar to those of nitric oxide (NO); therefore, the hypothesis of "EDRF = NO" is widely being accepted. NO is produced from L-arginine via catalysis by an enzyme that is activated by Ca2+. The enzyme activity is inhibited by L-monomethyl arginine and other L-arginine analogs. Chemical and physical stimulations increase intracellular Ca2+ in endothelial cells that seems to be associated with K(+)-channel opening and hyperpolarization. Current interests are directed to the possible roles of NO in the regulation of nerve function. There are evidences suggesting that NO modulates adrenergic nerve function in blood vessels and some brain cell functions regulated by cellular cyclic GMP. Particularly, NO may be a transmitter substance in non-adrenergic, non-cholinergic vasodilator nerves innervating the cerebral arteries. Future investigations will determine the physiological roles of EDRF or NO and its relationships to pathophysiology of vascular dysfunctions, such as vasospasm and those related to hypertension, diabetes, aging, etc., and the extended roles of NO in nerve function, inflammation, immune reactions, etc. would be clarified more extensively by accelerated progress in this field of research.
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PMID:[Endothelium-derived relaxing factor (EDRF)]. 216 93

Oxygen-free radical intermediates/scavengers were measured in 43 patients with essential hypertension who, although under antihypertensive therapy (without angiotensin-converting enzyme inhibitors), still had high blood pressure values. Measurements were taken before and 30, 60 and 120 min after sublingual administration of 25 mg captopril. Both systolic and diastolic blood pressures were reduced significantly. Twenty normotensive healthy volunteers were used as controls. The hypertensive patients had lower glutathione peroxide activity (GSHPx), higher superoxide dismutase (SOD) and serum glutathione reductase activity (GSHRx) compared with the controls. After captopril (30, 60 min) the glutathione and GSHPx increased compared with the pretreatment values. SOD and GSHRx remained high compared with the controls, while whole blood glucose-6-phosphate dehydrogenase remained low. Another group of 19 essential hypertensive patients, free of any antihypertensive medication (for at least 3 weeks), had lower GSHPx, SOD and higher GSHRx than the normal control group. Our results show significant differences in the oxygen free radical scavenger system of hypertensives compared with the normal subjects. It may be that captopril has a concomitant scavenging action together with its antihypertensive effect. Our study raises the question whether cell/organ damage will occur in hypertensive patients exposed to oxidative stress during periods of low antioxidative capacity.
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PMID:Oxygen free radical scavenger system intermediates in essential hypertensive patients before and immediately after sublingual captopril administration. 222 59

Severe experimental hypertension is associated with vascular hyperpermeability and cellular damage in small arteries and arterioles in rats. Oxygen-derived free radical production is also associated with increased vascular permeability and cellular injury in a variety of conditions, including ischemia-reperfusion and inflammation. To determine if free radicals play a role in the pathogenesis of hypertensive vascular disease, the free radical scavengers superoxide dismutase (SOD), catalase, SOD and catalase, and dimethyl sulfoxide (DMSO) were given to rats made acutely hypertensive with angiotensin II infusions. Untreated hypertensive and normotensive control animals were used for comparison. The effects of scavenger treatment were assessed by in vivo observations of intestinal small arteries by use of stereomicroscopy and videotape and light and transmission electron microscopy to identify and quantitate vascular lesions, and tracer particle injections to determine permeability changes. In vivo observations revealed that scavenger treatment did not alter vascular constriction patterns, vessel caliber, or blood pressures. Electron microscopy of arteries from untreated hypertensive rats showed more severe and more extensive endothelial and smooth muscle lesions, increased tracer particle penetration, and greater fibrin deposition than that found in scavenger-treated hypertensive groups. Quantitation of vascular lesions showed approximately equal reductions in smooth muscle necrosis (p less than 0.01) and fibrin deposition (p less than 0.05) in arteries from each of the scavenger-treated hypertensive groups. The results indicate that the free radical scavengers SOD, catalase, SOD-catalase, and DMSO inhibit (but do not prevent) vascular hyperpermeability and cellular damage during acute, angiotensin II--induced hypertension. These findings suggest that free radicals play a role in the pathogenesis of hypertensive vascular disease, probably by exacerbating the vascular changes initially triggered by an acute elevation in blood pressure.
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PMID:Role of oxygen-derived free radicals in acute angiotensin II--induced hypertensive vascular disease in the rat. 230 4

These studies determined whether superoxide dismutase (SOD), an oxygen free-radical scavenger, affects brain and lung vascular protein extravasation and water content after acute hypertension. Hypertensive vascular injury was induced in rats by bolus injection of norepinephrine. Vascular permeability was assessed with 125I-labeled serum albumin and water content determined by wet and dry weight measurement. Pretreatment with SOD prevented or reduced the increase in brain water content and brain and lung protein extravasation caused by hypertension, whereas inactivated SOD had no effect. SOD also reduced mortality caused by acute hypertension. Treatment 30 min after hypertension with SOD or polyethylene glycol-conjugated SOD reduced edema caused by hypertension. In some instances SOD reduced tissue water content and permeability to below normal control levels found in animals without hypertension. These studies show that oxygen radicals contribute to increases in permeability and water content after hypertensive injury and also suggest that oxygen radicals may contribute to regulation of vascular permeability and water content in normal animals.
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PMID:Superoxide dismutase reduces permeability and edema induced by hypertension in rats. 238 23

Clinical and experimental evidence demonstrates that hypertrophied cardiac tissue is more sensitive to ischemic injury than is normal myocardium. Recent studies indicate that cardiac ischemia-reperfusion injury involves the generation of toxic oxygen free radicals. We used the spontaneously hypertensive rat (SHR) model, with its otherwise genetically identical control (the Wistar-Kyoto [WKY] rat), to investigate the potential role of enzymes that generate and detoxify oxygen radicals in the sensitivity of hypertrophied heart to ischemia and reperfusion. Because hypertension develops progressively with age in SHRs, we assayed xanthine oxidase, superoxide dismutase, catalase, and glutathione peroxidase at three different time points and found significant fluctuations at different ages. At age 26 weeks, physiological measurements demonstrated hypertension and increased sensitivity to ischemia and reperfusion, measured as significantly decreased left ventricular recovery after injury. At this age, xanthine oxidase, which may generate oxygen radicals, was significantly increased in SHR compared with WKY rats (p = 0.003). Superoxide dismutase, which is a principal step in oxygen-radical detoxification, was significantly lower (p = 0.044). These data suggest that differences in the constitutive levels of oxygen-radical metabolic pathways are different in hypertrophied myocardium, and it is suggested that this finding may play a role in the response of these hearts to ischemia-reperfusion injury.
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PMID:Response to ischemia-reperfusion injury in hypertrophic heart. Role of free-radical metabolic pathways. 253 7

To determine if oxygen-derived free radicals are mediators of endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rats (SHR), the mechanism of contraction to xanthine plus xanthine oxidase was studied. Rings, with and without endothelium, of thoracic aorta from normotensive Wistar-Kyoto (WKY) rats and SHR were suspended in organ chambers for isometric tension recording. Oxygen-derived free radicals caused concentration-dependent contractions; these contractions were twice as large in the aortas of SHR than in WKY rats. Deferoxamine reversed the response to xanthine oxidase to a small relaxation. Either allopurinol, superoxide dismutase, or catalase, or the combination of superoxide dismutase plus catalase reduced the contractions. Diltiazem inhibited the response to xanthine oxidase; in contrast, phentolamine plus propranolol did not affect it. Indomethacin and meclofenamate, but not tranylcypromine or dazoxiben blocked the contractions. Endothelium-dependent contractions to acetylcholine in aortas from the SHR were not affected by deferoxamine or superoxide dismutase plus catalase. These data suggest that hydroxyl radicals cause contractions in the rat aorta, which are dependent on extracellular calcium and mediated by activation of the cyclooxygenase in the vascular smooth muscle. The augmented contractions in the hypertensive strain are due to an increased reactivity of the smooth muscle to oxygen-derived free radicals. However, the lack of effect of the scavengers on endothelium-dependent contractions to acetylcholine suggests that the endothelium-derived contracting factor is chemically different from oxygen-derived free radicals.
Hypertension 1989 Jun
PMID:Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. 256 6


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