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

Using electron microscopy and cytochemical techniques we investigated structures which are associated with long-term hypertension and ageing in the myocardial cell of the rat. Lysosomes, demonstrated by acid phosphatase and aryl sulfatase activities, were found mainly in the perinuclear region in young rats. With age these organelles appeared with increasing frequency in other regions of the cell. Spontaneously hypertensive rats (SHR) showed an earlier apparent migration of lysosomes than did normotensive rats (WKY). Our observations indicate that lysosomes were closely associated with autophagic vacuoles, membrane swirls , translucent mitochondria, myelin figures and other structures linked with degenerative events. In the oldest SHR lysosomes, autolysosomes (autophagic vacuoles with lysosomal activity), and degenerative structures were observed in various regions of the myocardial cell. Peroxisomes, as demonstrated by catalase activity, did not seem to be affected by hypertension or age. A number of dense osmophilic structures did not react for any of the enzymes studied; these included myelin figures, mitochondrial inclusions and diffuse dense bodies. Our observations implicate both ageing and hypertension in the enhancement of lysosomes and their end products.
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PMID:Cytochemistry of myocardial structures related to degenerative processes in spontaneously hypertensive and normotensive rats. 623 95

Hemin, in the presence of 2-mercaptoethanol and oxygen, catalyzes the selective degradation of heme-binding proteins to small peptide fragments. Among the proteins examined, the heme-binding protein of rabbit serum (HBP-93) proved to be unusually sensitive. Myoglobin also exhibited considerable sensitivity whereas hemopexin and bovine serum albumin were only slightly susceptible to this degradative action of hemin. The reaction with HBP-93 depended upon coordination of the protein with hemin, was optimal at pH 6.5 and increased 4-fold as the temperature was elevated from 10 to 60 degrees C. The requirement for both oxygen and the reducing agent, 2-mercaptoethanol, and the partial protection of HBP-93 to degradation by catalase, superoxide dismutase, mannitol, and thiourea suggest the involvement of reduced oxygen species in the reaction. A possible role for the heme-mediated degradation of proteins in cell differentiation and other biological responses is discussed.
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PMID:Hemin-mediated oxidative degradation of proteins. 632 3

The effects of topical application of agents which produce oxygen radicals on cerebral arterioles were studied in anesthetized cats. Xanthine oxidase plus xanthine, which produced superoxide anion radical, hydrogen peroxide, and hydrogen peroxide plus ferrous sulfate, which produced the free hydroxyl radical, induced sustained dilation, reduced responsiveness to the vasoconstrictor effect of hypocapnia, and destructive lesions of the endothelium and of the vascular smooth muscle. Similar effects were produced by arachidonate, 15-HPETE, and PGG2. The effect of arachidonate was inhibited by mannitol, a free hydroxyl radical scavenger, the effect of PGG2 was inhibited by SOD, the effect of 15-HPETE was inhibited by either catalase or SOD. These results suggest that these cerebral vascular abnormalities were produced by a single destructive free radical, probably the hydroxyl free radical, generated via interaction of superoxide and hydrogen peroxide. Cerebral vascular abnormalities similar to those produced by oxygen radicals were also seen after experimental concussive brain injury or after acute hypertension. After brain injury, activation of phospholipase C and increased brain prostaglandin concentration were demonstrated. The vascular effects of brain injury and acute hypertension were inhibited by free radical scavengers. The results suggest that, in these conditions, vascular damage is induced by oxygen radicals generated from arachidonate in association with increased prostaglandin synthesis.
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PMID:Oxygen radicals and vascular damage. 640 99

The subcellular distribution and nature of rat renal renin has been investigated by means of analytical subcellular fractionation and gel filtration on Sephadex G-100. During differential centrifugation, renin activity was recovered mainly in soluble and heavy mitochondrial fractions. On sucrose gradient centrifugation in either a conventional or in a B XIV zonal rotor, renin activity equilibrated at 1.54 M sucrose and was partially resolved from marker enzymes for mitochondria (succinate dehydrogenase), lysosomes (acid phosphatase), plasma membranes (alkaline phosphatase), and peroxisomes (catalase). On gel filtration of the soluble or extracts of the renin-granular fractions on Sephadex G-100, renin activity eluted as a single peak with an apparent molecular weight (MW) of 42,000; no change in activity was found when these fractions were acidified to pH 3.0. When kidney homogenates were prepared in the presence of the proteolytic inhibitor N-ethylmaleimide (NEM, 10 mM), whereas the renin from the granular fractions displayed a MW of 44,000, that from the soluble fraction was apparently higher (69,000). Addition of NEM (10 mM) to the soluble fraction previously shown to contain only the low MW form of renin also resulted in an apparently high MW form of renin. These results indicate that rat renal renin is associated with a mechanically fragile, distinct type of subcellular organelle. Renin within this structure is of the low MW form and is not acid activatable. The soluble fraction, however, contains a factor(s) that, in the presence of NEM, combines with the low MW renin to form a complex of apparently high MW.
Hypertension
PMID:Subcellular distribution and storage form of rat renal renin. 699 67

Platelet-activating factor (PAF) causes pulmonary hypertension and lung edema in animals and isolated perfused lungs by poorly understood mechanisms. Because oxidative mechanisms have been implicated in PAF-mediated cellular injury, we tested the hypothesis that superoxide anion (O2-.) contributes to PAF-induced lung injury by determining whether superoxide dismutase (SOD) could prevent the lung injury. Isolated rabbit lungs were perfused with PAF (100 nM) at a dose that caused transient hypertension and mild edema. Lungs pretreated with Cu,Zn SOD (100 U/ml) for 10 min developed persistent pulmonary hypertension and more lung edema formation in response to PAF. Enhanced responses to PAF also were observed in lungs perfused with 200 U/ml Cu,Zn SOD, but not with 10 or 40 U/ml Cu,Zn SOD. The higher doses of SOD also decreased thromboxane B2 levels in the perfusate. Potentiation of the PAF effect by Cu,Zn SOD was eliminated if the enzyme was inactivated or if the lung was treated with an anion channel blocker. The augmented PAF response in the presence of SOD was not altered by catalase (200 U/ml) or by nitric oxide synthase inhibitor. The data suggest that excessive Cu,Zn SOD enzyme activity potentiates PAF-induced injury in perfused rabbit lung presumably by overscavenging extracellular O2.- generated from intercellular sources. The augmented responses to PAF are not directly attributable to increased hydrogen peroxide, nitric oxide-related products, or thromboxane A2 production. These results suggest the new hypothesis that a balance between O2-. production and its metabolism determines vascular and endothelial responses to PAF.
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PMID:Superoxide dismutase potentiates platelet-activating factor-induced injury in perfused lung. 751 30

Previous studies have shown that exercise-induced changes in muscle antioxidant status occur shortly after exercise. The present studies were designed to determine if longer-term exercise-related changes in antioxidant enzyme activities in both normotensive (WKY) and hypertensive rats (SHR) occurred, and if these changes were related to the levels of lipid peroxidation. WKY and SHR rats were exercised over a 10-week period using a progressive treadmill regimen. After a 1-week detraining period, the animals were euthanized and measurements of tissue antioxidant enzyme activities and lipid peroxide levels were determined in both exercised and cage-sedentary groups. Decreases in antioxidant activities (particularly glutathione peroxidase and catalase) in liver, kidney, skeletal and cardiac were associated with exercise training in both WKy and SHR rats (e.g. left ventricular glutathione peroxidase specific activity in WKY rats was decreased from 234 +/- 25 [SD, n = 12] to 187 +/- 17 [SD, n = 11] units/mg protein). Elevations in activities of antioxidant enzymes were generally associated with hypertension in these tissues (e.g. left ventricular glutathione peroxidase specific activity in SHR rats was 275 +/- 30 [SD, n = 12] units/mg protein), but changes in activities were more variable than those seen in response to exercise. Exercise-related changes in tissue levels of thiobarbituric acid-reactive substances (an indirect measure of tissue lipid peroxide levels) generally did not correlate with exercise-related antioxidant enzyme activity changes, and hypertension had no effect on these levels except in liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antioxidant enzyme activities and lipid peroxidation levels in exercised and hypertensive rat tissues. 758 28

The hypothesis was tested that plasma from ischemic hindlimbs facilitates hypertension. Ischemia-induced hypertension was generated in rats by infrarenal aortic cross clamping for 5 h after which plasma was obtained from femoral vein blood. In vitro contractile activity of naive aortic rings incubated for 2 h in plasma collected from ischemic rats demonstrated reduced relaxation to acetylcholine and nitroglycerin. Methylene blue (10(-5) M) induced greater contraction in rings incubated in control vs. ischemic plasma, suggesting that endogenous guanylate cyclase activity is decreased by ischemic plasma. However, 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP) relaxed equally strips incubated in ischemic or control plasma. Acetylcholine-induced nitrite release was significantly lower in ischemic vs. control plasma-incubated strips (8.6 +/- 2.7 vs. 28.2 +/- 2.3 ng/10 mg tissue wt, respectively). The impaired relaxation to acetylcholine in ischemic plasma-incubated rings was significantly increased by L-arginine but not by prior treatment of ischemic plasma with heating or superoxide dismutase and catalase. These findings suggest the impaired relaxation is mediated through inhibition of the nitric oxide-cGMP pathway. Prolonged blunting of vasodilation by ischemic plasma may therefore contribute to maintenance of a sustained vasoconstriction and ischemic hypertension.
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PMID:Inhibition of vascular nitric oxide-cGMP pathway by plasma from ischemic hindlimb of rats. 763 55

The immune system of the spontaneously hypertensive rat is dysfunctional compared with that of normotensive control strains. Previous studies from our laboratory have shown that immunodepression in the spontaneously hypertensive rat was mediated by macrophages. The current study examines the mechanism for the depressed proliferative responses to concanavalin A typically observed by splenic mononuclear cells of spontaneously hypertensive rats. We tested various inhibitors of known macrophage products responsible for suppressing lymphoid function. The nitric oxide synthetase inhibitor NG-monomethyl L-arginine produced dose-dependent derepression of the proliferative responses of splenic mononuclear cells to concanavalin A. In contrast, indomethacin and catalase exhibited only weak derepression of the proliferative responses. Subsequent analysis showed that splenic mononuclear cells from spontaneously hypertensive rats generated greater nitric oxide levels than cells from Wistar-Kyoto rats, and nitric oxide levels were reduced when the inhibitor was added to splenic mononuclear cell cultures from spontaneously hypertensive rats. We further demonstrated that L-arginine is required for the development of the depressed mitogen-induced proliferative responses in these cells. Addition of L-arginine in excess of 10 microM to cultures diminished cell proliferation and increased nitric oxide. Polyclonal antibodies to murine interferon gamma reduced nitric oxide accumulation by approximately 50%, suggesting that interferon gamma is partially responsible for enhancing nitric oxide production in mitogen-stimulated splenic mononuclear cell cultures from spontaneously hypertensive rats. Thus, this study provides evidence that the immune depression observed in the spontaneously hypertensive rat is nitric oxide dependent.
Hypertension 1993 Feb
PMID:Nitric oxide mediates immune dysfunction in the spontaneously hypertensive rat. 767 89

Dietary effects of polyunsaturated fatty acids (PUFA) omega-3 on lipid peroxidation (LPO) and antioxidant system were studied in 73 patients with ischemic heart disease, hyperlipoproteinemia (HLPE) type IIa, IIb, IV and essential hypertension. Eiconol-enriched antiatherosclerotic diet has more potent hypolipidemic, hypotensive and thrombolytic action in association with inhibition of LPO, enhances SOD activity, keeps red cell catalase within normal. Vitamin E concentrations were not changed. It is suggested that eiconol addition to antiatherosclerotic diet causes no LPO induction and is pathognomonic for HLPE, hypertension and IHD patients.
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PMID:[Dietary effects of PUFA omega-3 on lipid peroxidation and antioxidant system in patients with IHD, hyperlipoproteinemia and hypertension]. 781 30

The changes of 10 enzymatic activities of cat retinas and their blood vessels under acute ocular hypertension were systematically observed by enzyme histochemical methods. These changes were induced by the damage caused by retinal ischemia-reperfusion. The activities of the free radical scavengers, catalase and hydrogen peroxidase, were decreased, demonstrating that the excess of free radicals is one of the essential causes of the injury. The principles of treatment are besides lowering of intraocular hypertension, during retinal ischemic stage, oxygen and nutrients needed urgently should be supplied through extra-vascular route and during reperfusion stage, free radical scavengers ought to be given.
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PMID:[Experimental studies on changes in retinal enzyme activities under acute ocular hypertension in cat eyes]. 784 15


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