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

Much interest in cicletanine, a novel antihypertensive drug, has grown because it uniquely stimulates prostacyclin (PGI2) production and may, thereby, provide further cardiovascular protection. We postulated that cicletanine may be an antioxidant, and assessed its ability to protect the kidney in Dahl salt-sensitive (Dahl S) rats on a high salt diet. Cicletanine eradicated in vitro a stable radical, DPPH, and decreased the lipid peroxidation both in rat brain homogenate and in a xanthine-xanthine oxidase (X-XOD) superoxide generating system. Furthermore, cicletanine attenuated the inhibition of PGI2 synthase activity by 15HPETE. However, cicletanine did not exhibit superoxide dismutase-like activity in X-XOD system, suggesting that it behaves primarily as a hydroxy radical scavenger. A 6 week cicletanine treatment reduced blood pressure in Dahl S rats fed a high salt diet, and ameliorated functional and morphological injury to the kidney. This attenuation of glomerular sclerosis correlated with the attenuation of lipid peroxidation in the kidney homogenate. These data indicate that cicletanine is an antioxidant that protects the kidney from salt-induced hypertension in Dahl salt-sensitive strain rats.
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PMID:Possible radical scavenging properties of cicletanine and renal protection in Dahl salt sensitive rats. 834 28

The endothelium plays a critical role in maintaining vascular tone by releasing vasoconstrictor and vasodilator substances. Endothelium-derived nitric oxide is a vasodilator that can be rapidly inactivated by superoxide (reaction rate constant, K = 3.6 x 10(9) L/mol per second). The measurement of nitric oxide concentration in biological systems is a challenging analytic problem because nitric oxide is also rapidly inactivated by Fe(II), Fe(III), and O2, all of which are found in great abundance in biological systems. To date, no currently used instrumental technique has been suitable for direct in situ measurement of NO in isolated resistance arteries. We designed the present study to perform for the first time direct in situ measurements of NO in rat mesenteric resistance arteries and to delineate the effects of hypertension on the release of NO and/or its interaction with superoxide. We describe here an adaptation of the recently published design of a porphyrinic sensor for direct in vitro measurement of NO in a single cell. The most significant advantage of this modified porphyrinic microsensor is that its small size makes it ideal for NO measurement in resistance arteries with an internal diameter of 200 microns or less. Small segments of the third-order branch of the mesenteric artery were isolated from normotensive Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats and placed in an organ chamber filled with Hanks' balanced salt solution buffer (2 mL, 37 degrees C). The tip of the porphyrinic microsensor was inserted into the lumen of an isolated vascular ring, and NO release was monitored in situ after maximal stimulation of NO synthase with the receptor-independent agonist calcium ionophore A23187 (10 mumol/L). Maximal surface concentration of NO measured after A23187 administration was significantly smaller in 15-week-old hypertensive rats (0.28 +/- 0.03 mumol/L, n = 10) than in age-matched normotensive rats (0.38 +/- 0.03 mumol/L, n = 10, P < .03). However, in the presence of the superoxide scavenger superoxide dismutase (100 U/mL), the peak NO level from the hypertensive rats was 0.37 +/- 0.04 mumol/L (n = 10), which was comparable to that observed for the normotensive rats in the absence and presence of superoxide dismutase. In summary, our results demonstrate that in rat mesenteric resistance arteries hypertension is associated with increased NO decomposition by superoxide, whereas NO release remains unaffected. This may be important in the pathogenesis of hypertension and its cardiovascular complications.
Hypertension 1996 Jan
PMID:Direct in situ measurement of nitric oxide in mesenteric resistance arteries. Increased decomposition by superoxide in hypertension. 859 84

We tested the hypothesis that angiotensin II-induced hypertension is associated with an increase in vascular .O2- production, and characterized the oxidase involved in this process. Infusion of angiotensin II (0.7 mg/kg per d) increased systolic blood pressure and doubled vascular .O2- production (assessed by lucigenin chemiluminescence), predominantly from the vascular media. NE infusion (2.75 mg/kg per d) produced a similar degree of hypertension, but did not increase vascular .O2- production. Studies using various enzyme inhibitors and vascular homogenates suggested that the predominant source of .O2- activated by angiotensin II infusion is an NADH/NADPH-dependent, membrane-bound oxidase. Angiotensin II-, but not NE-, induced hypertension was associated with impaired relaxations to acetylcholine, the calcium ionophore A23187, and nitroglycerin. These relaxations were variably corrected by treatment of vessels with liposome-encapsulated superoxide dismutase. When Losartan was administered concomitantly with angiotensin II, vascular .O2- production and relaxations were normalized, demonstrating a role for the angiotensin type-1 receptor in these processes. We conclude that forms of hypertension associated with elevated circulating levels of angiotensin II may have unique vascular effects not shared by other forms of hypertension because they increase vascular smooth muscle .O2- production via NADH/NADPH oxidase activation.
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PMID:Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. 862 76

Thirty two pregnancies with pregnancy-induced hypertension (PIH) and twenty seven control normal pregnancies were analysed with regard to maternal and fetal blood enzymatic antioxidants. In PIH maternal erythrocyte, platelet and serum blood and in umbilical cord blood levels of lipid peroxides were higher than in normal pregnancy. Also the activities of platelet and erythrocyte superoxide dismutase and glutathione peroxidase were lower in PIH women. The concentration of lipid peroxides was higher, and the activity of glutathione peroxidase were lower in umbilical cord elements of women with PIH, than corresponding values of women with normal pregnancy. We suggest that disturbances in antioxidant enzymatic system are involved in the pathogenesis of maternal PIH, and it may also have effects on the function of antioxidant status of the fetus.
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PMID:[Decreased activity of oxidoreductases in erythrocytes and blood platelets from venous and umbilical blood of women with pregnancy-induced hypertension]. 864 79

Heart and red blood cell endogenous antioxidant status and plasma lipids were investigated in hypertensive, 14-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Specific heart and red blood cell antioxidant enzyme activities, as well as the susceptibility of tissues to H2O2-induced glutathione (GSH) depletion and lipid peroxidation, were measured. Systolic blood pressure in SHR was greater than in WKY rats at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg (1 mmHg = 133.3 Pa); p < or = 0.05), confirming the presence of hypertension in SHR. Red blood cell catalase (CAT) and superoxide dismutase (SOD) activities were greater (p < or = 0.05) in SHR than WKY rats. Red blood cell CAT activity was positively correlated (r = +0.634; p = 0.026) with SOD, which in turn was correlated (r = +0.709; p = 0.049) with systolic blood pressure. Heart SOD activity was higher (p < or = 0.05) in SHR, while glutathione reductase (GSSG-Red) activity was lower (p < or = 0.05) than in WKY rats. This reduced ability to recycle GSH in the heart coincided with greater (p < or = 0.05) levels of H2O2-induced lipid oxidation products in SHR. Plasma total cholesterol and triacylglycerol levels were lower (p < or = 0.05) in SHR than WKY rats, with no visible signs of atherosclerosis in either SHR or WKY rats. In summary, hypertension in SHR was associated with alterations in antioxidant enzyme profiles of red blood cells and heart, with the latter showing an increased susceptibility to in vitro lipid oxidation. Although hypertension is a recognized factor in the development of human atherosclerosis, spontaneously hypertensive rats did not exhibit signs of aortic plaque, reflecting the resistance of this species to the development of atherosclerosis.
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PMID:Heart and red blood cell antioxidant status and plasma lipid levels in the spontaneously hypertensive and normotensive Wistar-Kyoto rat. 877 9

Oxy-free radicals may be involved in the pathogenesis of accelerated atherosclerosis in hypertension. We evaluated the direct antioxidant potential of probucol in hypertensive arteries by studying the spatial immunohistochemical distribution of three primary antioxidant enzymes (AEs). Nineteen normocholesterolemic New Zealand White rabbits were divided into two groups: normotensive controls (NT; n = 6) and 13 animals rendered hypertensive by surgical coarctation of abdominal aorta. The hypertensive group was subdivided into hypertensive alone (HT; n = 8) and hypertensive treated with 1% probucol (PO) for 9 weeks (HT-P; n = 5). Blood pressure rose significantly in both hypertensive groups (P < .005). At autopsy, both hypertensive groups showed similarly significant increases in mean arterial intima-media thickness (IMT) whether or not they were treated with probucol. However, only HT rabbits revealed significant increases in the intima-media depth penetration of glutathione peroxidase, superoxide dismutase, and catalase AEs. By contrast, in HT-P animals probucol produced significant reductions of immunostaining of all three AEs compared to the HT group (P < .05). Additionally, specific macrophage immunostaining revealed that the arterial wall of HT rabbits had numerous (10 to 12 per high power field) subintimal and medial macrophages as compared to the HT-P animals (1 to 2 per high power field). The blood pressure level correlated significantly with IMT in all three groups, but with depth penetration of the three AEs only in the NT and HT groups. Probucol, therefore, appears to act in concert with the native arterial antioxidant enzymes as a potent free radical scavenger to reduce oxidative stress and thus attenuate the macrophage invasive response in hypertensive arteries.
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PMID:Probucol suppresses oxidant stress in hypertensive arteries. Immunohistochemical evidence. 878 83

Shichimotsu-koka-to, a Chinese herb, is a medicine prescribed to treat patients with hypertension. We investigated the effects of Shichimotsu-koka-to on the lesions of stroke-prone spontaneously hypertensive rats (SHRSP). The SHRSP were given 1% or 2% Shichimotsu-koka-to solution (1 g/kg/day or 2 g/kg/day) instead of drinking water from 8 to 42 weeks of age. When the 2 g/kg/day Shichimotsu-koka-to was chronically administered to the SHRSP, their life span was significantly prolonged by prevention of stroke, but there was no effect on blood pressure. The Shichimotsu-koka-to treatment decreased superoxide dismutase (SOD) activities in the cytosol of the cerebral cortex and increased SOD activities in the cytosol of the brain stem. The treatment with 2 g/kg/day Shichimotsu-koka-to decreased xanthine oxidase (XOD) activities in the cytosol of the cerebral cortex, and Shichimotsu-koka-to quenched superoxide anion (O2-) as determined by electron spin resonance analysis in vitro. In addition, SOD activities in the cytosol of the cerebral cortex of SHRSP not administered Shichimotsu-koka-to were increased by the drug in vitro. XOD activities in the cytosol of the cerebral cortex of SHRSP not administered Shichimotsu-koka-to were inhibited by this herb in vitro. These results suggest that these preventive effects of Shichimotsu-koka-to on the stroke in SHRSP are due its ability to scavenge O2- and to inhibit O2- production by the hypoxanthine-XOD system in the cytosol of the cerebral cortex.
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PMID:[Shichimotsu-koka-to prevents stroke and changes free-radical-related enzymes in stroke-prone spontaneously hypertensive rats (SHRSP)]. 881 Apr 92

Although endothelium-dependent vasodilation is impaired in human hypertension, the mechanism underlying this abnormality is not yet completely elucidated. It has been suggested that accelerated inactivation of nitric oxide (NO) due to superoxide anion, which is rapidly removed by superoxide dismutase (SOD) in physiological condition, may be related to hypertension. Therefore, SOD deficiency following an increase in superoxide anion production contributes to a rise in arterial blood pressure (BP). We hypothesized that there is defective endogenous SOD in patients with essential hypertension. To examine this assumption we measured the SOD activities of the erythrocytes in 335 healthy Chinese volunteers (age 2-76 years) and 30 hypertensive patients (age 60-75 years). The SOD activities of the healthy volunteers exhibited decreased trend with advancing aging. There was no significant difference in the SOD activities between men and women in each group. There is significant difference in the SOD activities (1814.35 +/- 250.00 vs 1584.06 +/- 126.19 u/Hb.g; P < 0.001) between the two groups (age 20-59 years; mean age 34 years vs age 60-76 years; mean age 67 years). The SOD activities in patients with essential hypertension were 1322.4 +/- 139.5 u/Hb.g and significantly lower than the corresponding healthy controls (P < 0.05). In the hypertensives, the SOD activities against systolic and diastolic arterial pressure seem to be shown the trend of negative correlation but did not reach the statistical significance. We conclude that the SOD activities in the erythrocytes are reduced in subjects with essential hypertension and increasing aging. The present findings, in a limited data, could suggest that the fall in SOD activities following an increased superoxide anion production with subsequently augmented NO inactivation is, at least in part, involved in the pathogenesis of human hypertension, although the evidence is indirect. The decrease in erythrocyte SOD activities may serve as a function of human aging.
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PMID:Increased superoxide anion production in humans: a possible mechanism for the pathogenesis of hypertension. 881 4

High levels of glycosylated human hemoglobin impair nitric oxide-mediated responses. However, the percentage of glycosylation for which this effect is observed and the mechanisms involved are unknown. We tested endothelium-dependent relaxations caused by acetylcholine in rat aortic segments either in control conditions or after preincubation with increasing percentages of glycosylated human hemoglobin. Human hemoglobin (1 and 10 nmol/L) inhibited endothelium-dependent relaxations only when glycosylated at 9% or higher. We evaluated the effect of 14% glycosylated human hemoglobin on acetylcholine-evoked responses in vessels preincubated with scavengers of superoxide anions, hydroxyl radical, or hydrogen peroxide (superoxide dismutase, deferoxamine, and catalase, respectively); with inhibitors of xanthine oxidase, cyclooxygenase, or thromboxane synthase (allopurinol, indomethacin, and dazoxiben, respectively); with blockers of thromboxane A2/prostaglandin H2 or endothelin receptors (SQ 30741 and BQ-123); and with the precursor of nitric oxide synthesis L-arginine. Superoxide dismutase abolished the effect of glycosylated hemoglobin, and the other substances did not have any effect. Glycosylated hemoglobin at 14% did not modify either the vasoconstrictions induced by the blocker of nitric oxide synthase NG-nitro-L-arginine methyl ester or the relaxations evoked in deendothelialized vessels by sodium nitroprusside and 8-bromo-cGMP. However, it inhibited the vasodilations evoked by exogenous nitric oxide. Superoxide dismutase abolished this latter effect. We conclude that the threshold for glycosylated human hemoglobin (Hb A1) to inhibit endothelium-dependent relaxation is 9%. This effect is due to interference with endothelial nitric oxide by means of superoxide anion production.
Hypertension 1996 Oct
PMID:Impairment of endothelium-dependent relaxation by increasing percentages of glycosylated human hemoglobin. Possible mechanisms involved. 884 82

Reactive oxygen species, such as superoxide and nitric oxide (NO), have been postulated to underlie the pathogenesis of various diseases. About 3 to approximately 10% of the oxygen utilized by tissues is converted to its reactive intermediates that impair cells and tissues. However, only a limited information supporting this hypothesis is available predominantly because of the short half life of these intermediates. To elucidate the role of superoxides and related metabolites in the pathogenesis of various diseases, two superoxide dismutase derivatives were synthesized; one (SM-SOD) circulates bound to albumin and accumulates in tissues with decreased pH and the other (HB-SOD) binds to vascular endothelial cells by a heparin-inhibitable mechanism. NO was first recognized as a potent vasorelaxant. NO rapidly diffuses across cells and binds to various proteins, such as guanylate cyclase, thereby modulating cellular metabolism. Because NO also reacts with superoxide and molecular oxygen, the two molecules might be major determinants of its half life and strongly affect its biological functions. In fact, targeting HB-SOD to vascular endothelial cells increased the cGMP levels in arterial walls and normalized the blood pressure of animals with genetic and nongenetic hypertension. Thus, the imbalance between superoxide and NO seems to underlie the pathogenesis of hypertension. NO forms a dissociable complex with cytochrome c oxidase in mitochondria and regulates cellular energy metabolism particularly under physiologically low oxygen tensions. Thus, cross-talk between oxygen, NO and superoxide radicals might play a critical role in regulating circulation and energy metabolism. Oxidative stress causes an imbalance in this cross-talk and underlies the pathogenesis of various diseases.
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PMID:[Role of oxidative stress in health and disease]. 893 79


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