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

We have recently reported that exaggerated oxidative stress in the renal medulla due to superoxide dismutase inhibition resulted in a reduction of renal medullary blood flow and sustained hypertension. The present study tested the hypothesis that selective scavenging of O2*- in the renal medulla would prevent hypertension associated with this exaggerated oxidative stress. An indwelling, aortic catheter was implanted in nonnephrectomized Sprague-Dawley rats for daily measurement of arterial blood pressure, and a renal medullary interstitial catheter was implanted for continuous delivery of the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC, 7.5 mg x kg(-1) x d(-1)) and a chemical superoxide dismutase mimetic, 4-hydroxytetramethyl piperidine-1-oxyl (TEMPOL, 10 mg. kg-1. d-1). Renal medullary interstitial infusion of TEMPOL completely blocked DETC-induced accumulation of O2*- in the renal medulla, as measured by the conversion rate of dihydroethidium to ethidium in the dialysate and by urinary excretion of 8-isoprostanes. However, TEMPOL infusion failed to prevent DETC-induced hypertension, unless catalase (5 mg x kg(-1) d(-1)) was coinfused. Direct infusion of H2O2 into the renal medulla resulted in increases of mean arterial pressure from 115+/-2.5 to 131+/-2.1 mm Hg, which was similar to that observed in rats receiving the medullary infusion of both TEMPOL and DETC. The results indicate that sufficient catalase activity in the renal medulla is a prerequisite for the antihypertensive action of TEMPOL and that accumulated H2O2 in the renal medulla associated with exaggerated oxidative stress might have a hypertensive consequence.
Hypertension 2003 Jul
PMID:Increased renal medullary H2O2 leads to hypertension. 1278 42

In 20 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of a new compound, applied onto the skin (Crystacide) were assessed in a randomized, controlled study. Duplex scanning was used to assess the presence of venous obstruction and incompetence, and microcirculatory methods were used to assess and quantify venous microangiopathy and to follow up subjects after local treatment with Crystacide. Laser Doppler flowmetry (LDF) was used to assess skin perfusion in association with transcutaneous (tc) partial pressure of oxygen (PO2) measurements. Local plasma free radicals (PFR) were evaluated in the area surrounding the venous ulcer, with the D-Rom test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatment: PO2 was increased, PFR and LDF were decreased (flux increase is associated with venous hypertension), and the ulcer area was significantly smaller at 10 days in the Crystacide group in comparison with the placebo group (p<0.05). In conclusion, in venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals improving healing.
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PMID:Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide. Evaluation of free radicals, laser Doppler flux and PO2. A prospective-randomized-controlled study. 1278 25

A membrane-permeable SOD mimetic, 4-hydroxytetramethyl-piperidine-1-oxyl (tempol), has been used as an antioxidant to prevent hypertension. We recently found that this SOD mimetic could not prevent development of hypertension induced by inhibition of renal medullary SOD with diethyldithiocarbamic acid. The present study tested a hypothesis that increased H2O2 counteracts the effects of tempol on renal medullary blood flow (MBF) and Na+ excretion (UNaV), thereby restraining the antihypertensive effect of this SOD mimetic. By in vivo microdialysis and Amplex red H2O2 microassay, it was found that interstitial H2O2 levels in the renal cortex and medulla in anesthetized rats averaged 55.91 +/- 3.66 and 102.18 +/- 5.16 nM, respectively. Renal medullary interstitial infusion of tempol (30 micromol x min-1x kg-1) significantly increased medullary H2O2 levels by 46%, and coinfusion of catalase (10 mg x min-1x kg-1) completely abolished this increase. Functionally, removal of H2O2 by catalase enhanced the tempol-induced increase in MBF, urine flow, and UNaV by 28, 41, and 30%, respectively. Direct delivery of H2O2 by renal medullary interstitial infusion (7.5-30 nmol x min-1x kg-1) significantly decreased renal MBF, urine flow, and UNaV, and catalase reversed the effects of H2O2. We conclude that tempol produces a renal medullary vasodilator effect and results in diuresis and natriuresis. However, this SOD mimetic increases the formation of H2O2, which constricts medullary vessels and, thereby, counteracts its vasodilator actions. This counteracting effect of H2O2 may limit the use of tempol as an antihypertensive agent under exaggerated oxidative stress in the kidney.
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PMID:Increased H(2)O(2) counteracts the vasodilator and natriuretic effects of superoxide dismutation by tempol in renal medulla. 1279 86

Although the cyclic AMP response element-binding protein (CREB) plays an important role in the survival of neuronal cells and T lymphocytes, the role of CREB in vascular smooth muscle cells (VSMCs) is incompletely characterized. We examined the role of CREB in VSMCs stimulated with reactive oxygen species. Activation of CREB was examined by Western blot analysis with an antibody that specifically recognizes phosphorylation at serine 133 of CREB, which is a critical marker of activation. Hydrogen peroxide (H2O2) time-dependently induced phosphorylation of CREB, with a peak at 15 minutes. The H2O2-induced phosphorylation of CREB was partially blocked by inhibition of either extracellular signal-regulated protein kinase kinase by PD98059 or of p38 mitogen-activated protein kinase (MAPK) by SB203580. AG1478, an epidermal growth factor receptor (EGFR) inhibitor, suppressed the H2O2-induced phosphorylation of CREB and tyrosine phosphorylation of EGFR. Overexpression of the dominant-negative form of CREB by an adenovirus vector suppressed H2O2-induced c-fos expression. These findings suggest that H2O2 induces CREB phosphorylation through EGFR transactivation and mitogen-activated protein kinase pathways. CREB might be a novel redox-sensitive transcription factor involved in the regulation of VSMC gene expression.
Hypertension 2003 Aug
PMID:Cyclic AMP response element-binding protein mediates reactive oxygen species-induced c-fos expression. 1281 Jul 57

Hypertension is an age-dependent disorder. Oxidative stress has been suggested to play a role in aging and age-dependent disorders. The objective of this study is to examine the oxidant and antioxidant status in the aorta of a mouse model with high blood pressure (BPH). Our results showed that the level of malondialdehyde (MDA) in the aorta of BPH mice was approximately 2.6-fold higher than that of the normal blood pressure (BPN) mice, suggesting an increased in vivo oxidative stress in the arterial wall of BPH mice. In addition, the release of hydrogen peroxide (H2O2) from the aorta of BPH mice was significantly faster than that of BPN mice. To determine if the increased H2O2 release is related to a down-regulation of antioxidant enzymes in the arterial wall, we measured the activities of the major antioxidant enzymes in mouse aortas. We observed that the activities of Cu/Zn-superoxide dismutase (SOD) and glutathione peroxidase-1 in BPH mice were similar to BPN mice. On the other hand, the catalase activity in the aorta of BPH mice was significantly reduced while the activities of Mn-SOD and extracellular (EC)-SOD in the aorta of BPH mice were significantly elevated as compared with BPN mice. These results suggest that increase in SOD activity and decrease in catalase activity might be responsible for the increased release of H2O2 in the arterial wall of BPH mice.
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PMID:Elevation of oxidative stress in the aorta of genetically hypertensive mice. 1287 44

Both insulin resistance and reactive oxygen species (ROS) have been reported to play essential pathophysiological roles in cardiovascular diseases, such as hypertension and atherosclerosis. However, the mechanistic link between ROS, such as H2O2 and insulin resistance in the vasculature, remains undetermined. Akt, a Ser/Thr kinase, mediates various biological responses induced by insulin. In this study, we examined the effects of H2O2 on Akt activation in the insulin-signaling pathway in vascular smooth muscle cells (VSMCs). In VSMCs, insulin stimulates Akt phosphorylation at Ser473. Pretreatment with H2O2 concentration- and time-dependently inhibited insulin-induced Akt phosphorylation with significant inhibition observed at 50 microM for 10 min. A ROS inducer, diamide, also inhibited insulin-induced Akt phosphorylation. In addition, H2O2 inhibited insulin receptor binding partially and inhibited insulin receptor autophosphorylation almost completely. However, pretreatment with a protein kinase C inhibitor, GF109203X (2 microM), for 30 min did not block the inhibitory effects of H2O2 on insulin-induced Akt phosphorylation, suggesting that protein kinase C is not involved in the inhibition by H2O2. We conclude that ROS inhibit a critical insulin signal transduction component required for Akt activation in VSMCs, suggesting potential cellular mechanisms of insulin resistance, which would require verification in vivo.
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PMID:Hydrogen peroxide inhibits insulin signaling in vascular smooth muscle cells. 1287 3

The Na+/Ca2+ exchanger regulates intracellular calcium ([Ca2+]i), and attenuation of Na+/Ca2+ exchange by oxidative stress might lead to dysregulation of [Ca2+]i. We have shown that the Na+/Ca2+ exchanger differs functionally and at the amino acid level between salt-sensitive and salt-resistant rats. Therefore, the purpose of these studies was to determine how oxidative stress affects the activities of the 2 Na+/Ca2+ exchangers that we cloned from mesangial cells of salt-resistant (RNCX) and salt-sensitive (SNCX) Dahl/Rapp rats. The effects of oxidative stress on exchanger activity were examined in cells expressing RNCX or SNCX by assessing 45Ca2+ uptake (reverse mode) and [Ca2+]i elevation (forward mode) in the presence and absence of H2O2 and peroxynitrite. Our results showed that 45Ca2+ uptake in SNCX cells was attenuated at 500 and 750 micromol/L H2O2 (63+/-12% and 25+/-7%, respectively; n=16) and at 50 and 100 micromol/L peroxynitrite (47+/-9% and 22+/-9%, respectively; n=16). In RNCX cells, 45Ca2+ uptake was attenuated at only 750 and 100 micromol/L H2O2 and peroxynitrite (61+/-9% and 63+/-6%, respectively; n=16). In addition, the elevation in [Ca2+]i was greater in SNCX cells than in RNCX cells in response to 750 micromol/L H2O2 (58+/-5.5 vs 17+/-4.1 nmol/L; n=13) and 100 micromol/L peroxynitrite (33+/-5 vs 11+/-6 nmol/L; n=19). The enhanced impairment of SNCX activity by oxidative stress might contribute to the dysregulation of [Ca2+]i that is found in this model of salt-sensitive hypertension.
Hypertension 2003 Sep
PMID:Na+/Ca2+ exchanger: target for oxidative stress in salt-sensitive hypertension. 1288 89

The suggested involvement of ouabain in hypertension raised the need for a better understanding of its cellular action, but the mechanisms of ouabain toxicity are only now being uncovered. In the present study, we show that reduced glutathione (GSH) protected ouabain-sensitive (OS) cells from ouabain-induced toxicity and that the inhibition of GSH synthesis by D, L-buthionine-(S,R)-sulfoximine (BSO) sensitized ouabain-resistant (OR) cells. We could not observe formation of *OH or H2O2, but there was an increase in O2*-only in OS cells. Unexpectedly, an increased number of OR cells depolarized after treatment with ouabain, and BSO blocked this depolarization. Moreover, GSH increased ouabain-induced depolarization in OS cells. A sustained increase in tyrosine phosphorylation (P-Tyr) and Ras expression was observed after treatment of OS cells, and GSH prevented it. Conversely, BSO induced P-Tyr and Ras expression in ouabain-treated OR cells. The results obtained have three major implications: There is no direct correlation between membrane depolarization and ouabain-induced cell death; ouabain toxicity is not directly related to its classical action as a Na+, K+-ATPase inhibitor but seems to be associated to signal transduction, and GSH plays a major role in preventing ouabain-induced cell death.
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PMID:Mechanisms of ouabain toxicity. 1295 81

Insulin resistance is associated with vascular disease. Physiological concentrations of insulin inhibit cultured vascular smooth muscle cell (VSMC) contraction and migration by increasing nitric oxide (NO)-stimulated cGMP accumulation. The failure to do so in insulin-resistant states may aggravate vascular disease. We sought to determine the mechanism of insulin's increase in cGMP accumulation. Isobutylmethylxanthine, an inhibitor of phosphodiesterase activity, inhibited the decline in cGMP levels measured by immunoassay in cGMP-loaded cultured rat aortic VSMCs, but 1 nmol insulin did not. Thus, insulin's increase in cGMP accumulation is due to stimulated production, not inhibited hydrolysis and/or efflux. Insulin, which increases the NADH/NAD+ ratio in these cells, stimulated superoxide anion (O2-) accumulation measured by lucigenin luminescence to 256+/-25% (P<0.05) by a process that was blocked by the NADH oxidase inhibitor diphenyliodonium (DPI) and enhanced by the superoxide dismutase inhibitor diethyldithiocarbonate (DETCA). Insulin also stimulated hydrogen peroxide (H2O2) accumulation measured by horseradish peroxidase/luminol luminescence to 221+/-22% (P<0.05) by a DETCA-sensitive mechanism. H2O2 (100 micromol/L) in the absence of insulin increased NO-stimulated cGMP accumulation to 151+/-11% (P<0.05). Insulin alone increased NO-stimulated cGMP accumulation to 183+/-17% (P<0.05), and this was blocked by either DPI or DETCA. We conclude that insulin increases NADH oxidase-derived O2- production in cultured rat VSMCs. This did not cause the expected scavenging of NO resulting in the reduction of NO-stimulated guanylate cyclase activity, but enough O2- was metabolized to H2O2 to increase overall NO-stimulated cGMP production.
Hypertension 2003 Oct
PMID:Insulin-stimulated hydrogen peroxide increases guanylate cyclase activity in vascular smooth muscle. 1296 80

Preeclampsia is a leading cause of maternal and neonatal mortality and morbidity. It is a complex syndrome of undetermined etiologic origin, usually diagnosed during the second half of pregnancy, with clinical features of hypertension, proteinuria, and edema. No cure for preeclampsia exists, except premature delivery. There is increasing evidence that oxidative stress is an important contributing factor to the pathogenesis of preeclampsia. Oxidative stress is defined as an imbalance between reactive oxygen species (ROS), such as nitric oxide (NO*), superoxide anion (O2*-), and hydrogen peroxide (H2O2), and antioxidants, favouring an overabundance of ROS. The consequence of an overproduction of ROS can be observed as increased levels of markers of oxidative stress, such as lipid peroxides. Pregnant women affected by preeclampsia may have abnormal ROS production, particularly NO* and O2*-, abnormal levels of antioxidant defences, and increased placental lipid peroxidation. Several observations suggest that decreased bioavailability of endothelium-derived NO*, due to oxidative destruction of NO* by ROS, might contribute to the impaired endothelium-dependent vasodilatory responses and multisystemic pathology of preeclampsia, a phenomenon in which antioxidant vitamins may play a beneficial role. This review focuses on the rationale for vitamins C and E supplementation toward prevention of preeclampsia, with an emphasis on the limit of our scientific knowledge concerning the deleterious oxidative events taking place in this pathology.
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PMID:Current concepts in the use of antioxidants for the treatment of preeclampsia. 1297 Aug 9


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