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

Deposits of amyloid beta-peptide (A beta) in senile plaques and cerebral blood vessels is the prominent feature of Alzheimer's disease (AD), regardless of genetic predisposition. The cellular origin of cerebral deposits of A beta or its precise role in the neurodegenerative process has not been established. Recently we demonstrated a novel action of beta-amyloid on blood vessels--vasoactivity and endothelial damage through superoxide radicals. Since endothelial dysfunction is associated with vascular degenerative diseases, we examined the direct action of A beta on endothelial cells in culture. Cells treated with A beta displayed characteristics of necrotic cell death which was prevented by the free radical scavenging enzyme superoxide dismutase. Stimulation of endothelial nitric oxide (NO) production by the calcium ionophore, A23187, or bradykinin was inhibited by beta-amyloid. We conclude that an imbalance of NO and oxygen radicals may mediate the A beta-induced endothelial damage on endothelial cells in culture and may also contribute to a variety of pathophysiological conditions associated with aging: hypertension, cerebral ischemia, vasospasm, or stroke.
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PMID:beta-amyloid-induced endothelial necrosis and inhibition of nitric oxide production. 902 96

The activities of glomerular intrinsic antioxidant enzymes (AOEs) were measured in a diabetic spontaneously hypertensive rat (SHR) model. The effects of antihypertensive drugs, i.e. captopril or triple therapy (hydralazine, reserpine, and hydrochlorothiazide), on glomerular intrinsic AOE activities in this model were evaluated. The effects of blood glucose control on the AOE activities were also determined. The aim of the present study was to determine whether activities of glomerular intrinsic AOEs might correlate with disease activity in diabetic SHR. This study showed a decrease of glomerular intrinsic AOE, i.e. Cu/Zn-SOD and Mn-SOD (SOD = superoxide dismutase), glutathione peroxidase, and catalase, activities in diabetic SHR. Glomerular Cu/Zn-SOD or Mn-SOD, glutathione peroxidase, and catalase activities in nondiabetic SHR were slightly lower than those in nondiabetic WKY rats. These activities in diabetic SHR were significantly improved after captopril or triple therapy or blood glucose control. The levels of urinary albumin excretion, creatinine clearance, and glomerular tuft areas in diabetic SHR were also improved after the therapy. It appears that hypertension and hyperglycemia may influence the glomerular intrinsic AOE activities, albuminuria, creatinine clearance, and glomerular tuft areas in diabetic SHR. Thus, it is indicated that control of blood pressure or blood glucose is a very important factor for preventing renal injuries in the diabetic SHR model.
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PMID:Effects of antihypertensive drugs or glycemic control on antioxidant enzyme activities in spontaneously hypertensive rats with diabetes. 922 34

The premature presence of senile plaques (SP) in coronary artery disease (CAD), and neurofibrillary tangles (NFT) as well as SP in hypertension (HyperT), suggest a neuropathologic link between CAD, HyperT, and AD. Previous MI, CAD and HyperT often occur in and may increase the risk of AD. Expression of Apo-E4 likely increases risk of CAD by elevating blood cholesterol and the risk of AD via proposed interactions with beta-amyloid and/or free radicals (FRs). Any Apo-E4 effect is vague, but FRs probably mediate vascular damage in HyperT. Increasing FR content in the blood is related to increasing CAD severity, while the severity of elevated FR level correlates with how deep into a blood vessel there is activation of the FR scavenger enzyme, superoxide dismutase (SOD). The ApoE genotype and SP/NFT areal densities were determined in a large population of non-demented CAD, HyperT and non-heart disease (non-HD) control subjects, and compared to findings in a similar number of AD patients. ApoE immunoreactivity was determined in many individuals. Cholesterol content in cortex was determined by HPLC in a small, loosely age-matched group of Apo-E4 genotype-matched AD, CAD and non-HD subjects. SOD immunoreactivity was also assessed in a number of subjects. The Apo-E4 genotype frequency was increased in CAD, HyperT and AD compared to non-HD controls. Dose of Apo-E4 correlated with SP densities, but not NFT, and only in the non-demented groups. Essentially all SP in CAD, HyperT and non-HD subjects were ApoE-immunoreactive. Cortical cholesterol was increased in CAD and AD compared to controls. SOD immunoreactivity was similar in HyperT and AD; SP were immunodecorated in both. AD, CAD and HyperT may be linked, while CAD and HyperT subjects may die of heart disease before showing cognitive change.
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PMID:Coronary artery disease, hypertension, ApoE, and cholesterol: a link to Alzheimer's disease? 932 86

We investigated the effects of aging, a cardiovascular risk factor, on vascular function with regard to endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), and endothelin (ET-1) in aorta and femoral artery of the rat. Concentration-response curves to acetylcholine, calcium ionophore A23187, norepinephrine, ET-1, big endothelin, sodium nitroprusside, and exogenous SOD were obtained. Expression of eNOS mRNA was analyzed by reverse-transcription polymerase chain reaction, SOD activity was assessed using a chemiluminescence-based cytochrome c assay, and ET-1 plasma concentrations were measured by radioimmunoassay. In aorta of old rats, relaxations to acetylcholine and calcium ionophore A23187, basal NO release, and expression of eNOS mRNA in aortic endothelial cells were reduced (P<.05). In femoral arteries, relaxations to acetylcholine were preserved, whereas basal release of NO was attenuated (P<.05). Aging selectively increased contractions to norepinephrine and functional endothelin converting enzyme activity and attenuated contractions to ET-1 in aortas but not femoral arteries. Vascular SOD activity was higher in the femoral artery (P<.05) and unaffected by aging. Plasma ET-1 levels increased and plasma SOD activity decreased with age (P<.05). Aging was associated with an anatomic heterogeneity of endothelial dysfunction, functional endothelin converting enzyme activity, and vascular SOD activity. Vascular function was impaired in the aorta but not the femoral artery, which may be related to lower eNOS mRNA expression and SOD activity. These data suggest differential regulation of the vascular aging process that may contribute to the anatomic heterogeneity of atherosclerosis.
Hypertension 1997 Oct
PMID:Anatomic heterogeneity of vascular aging: role of nitric oxide and endothelin. 933 78

Both endothelial cells and vascular smooth muscle cells are capable of producing reactive oxygen species from a variety of enzymatic sources. In disease states such as atherosclerosis and hypertension, vascular production of these reactive oxygen metabolites can increase substantially. Increases in the production of superoxide anion can lead to decreases in ambient levels of nitric oxide via a facile radical/radical reaction that occurs more rapidly than the reaction of superoxide anion with superoxide dismutase. This phenomenon alters endothelial regulation of vasomotion in a variety of disease conditions. Recent evidence suggests that the major source of vascular superoxide ion and hydrogen peroxide is a membrane-bound, reduced nicotinamide-adenine dinucleotide (NADH)-dependent oxidase. The activity of this enzyme system is regulated by angiotensin II and is elevated following prolonged exposure to nitroglycerin. Alterations of vascular oxidant state caused by angiotensin II may contribute substantially to vascular pathology and may also provide a link between hypertension and atherosclerosis.
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PMID:Endothelial function and oxidant stress. 942 47

In order to elucidate the relationships between Zn and Cu and blood pressure, the present case-control study was carried out. Zn and Cu status was evaluated in 60 subjects, pharmacologically untreated, affected by mild stable hypertension and in 60 normotensives matched for sex, age and smoking habits. Different markers of Zn and Cu status, including serum, erythrocyte and urine levels of the two trace elements and activities of some Zn- or Cu-dependent enzymes (alkaline phosphatase, lactic dehydrogenase, superoxide dismutase and lysyl oxidase) were evaluated. No significant difference between hypertensives and normotensives was observed in the mean levels of Zn and Cu as well as in Zn- or Cu-dependent enzymes, though higher levels of serum copper were associated with increased risk of hypertension. Interesting relationships between the biological parameters investigated were observed in the hypertensive subjects. Inverse correlations between blood pressures and serum Zn were observed. Furthermore, blood pressure was inversely related to lysyl oxidase activity. These findings give further support to the hypothesis that an imbalance of Zn and Cu bioavailability may be associated to hypertensive condition.
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PMID:Zinc and copper status and blood pressure. 963 5

Inhaled nitric oxide (NO) is an important new therapeutic agent used to treat pulmonary arterial hypertension in a variety of disease states. However, the effects of NO on cells in the lung are uncertain. Previously, we have shown that NO gas depresses neutrophil oxidative cell function and increases neutrophil cell death. The purpose of this in vitro study was to determine the mechanism of neutrophil death. We hypothesized that NO hastened cell death by inducing apoptosis. To mimic the clinical environment of patients with respiratory failure, we also studied the effects of hyperoxia on neutrophil cell viability and apoptosis. Isolated human neutrophils were exposed to 80% O2 (O2), NO at 20 ppm in room air (NO/RA), 20 ppm NO blended with 80% O2 (NO/O2), or RA alone (control) for 2 to 24 h. Experiments were repeated with NO concentrations of 5 and 50 ppm and with 20 ppm in the presence of superoxide dismutase (SOD). Neutrophils were also incubated in the absence or presence of neutrophil stimulant fMLP (10 nM). Neutrophil cell viability was measured by fluorescence viability/cytotoxicity assay. Neutrophil apoptosis was assessed by cell death detection ELISA for histone-associated DNA fragments, TdT transferase-mediated fluorescence-labeled dUTP nick end labeling (TUNEL) assay, and DNA fragmentation gel electrophoresis. NO/O2-exposed neutrophils showed decreased viability at 2 h (31.7 +/- 3.7%, mean % viability +/- SD) compared with control (94.7 +/- 4.7%), O2 (75.6 +/- 9.3%), and NO/RA (62.8 +/- 14.9%; P < 0.05 by ANOVA; n = 9). Although control neutrophils demonstrated marked apoptosis at 24 h, there was no significant apoptosis at 2, 4, or 6 h (P < 0.001 by Kruskal-Wallis, n = 20) as assessed by ELISA and TUNEL assays. When compared with RA controls at 2 h, neutrophils exposed to NO/O2 showed significantly more apoptosis (292% of control, range: 106 to 2,488%, P < 0.001 by ANOVA and Kruskal-Wallis) but not with exposure to NO/RA or O2 alone. These findings were confirmed by TUNEL assay (n = 4, P < 0.05). NO/ RA and NO/O2-exposed neutrophils demonstrated both evidence of necrosis and enhanced DNA fragmentation at 2 h by gel electrophoresis (n = 2). Fifty parts per million NO produced similar findings, but exposure to 5 ppm NO did not induce significant DNA fragmentation. Coincubation with SOD inhibited NO/ O2-associated apoptosis, suggesting peroxynitrite contributed to cell death. Stimulation with fMLP did not alter apoptosis induced in neutrophils exposed to NO/RA or NO/O2. We conclude that exogenous NO gas, at clinically relevant concentrations under hyperoxic conditions, induces cell death in neutrophils in part by enhancing DNA fragmentation.
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PMID:Exogenous nitric oxide enhances neutrophil cell death and DNA fragmentation. 949 Jun 60

We tested the hypothesis that oxidative stress, mediated by dietary vitamin E deprivation, would alter vascular function through the interaction of oxygen-derived free radicals and nitric oxide (NO). This interaction may play an important role in the vascular pathophysiology of many diseases associated with oxidative stress. Mesenteric arteries from control (n = 12) and vitamin E-deprived (n = 12) Sprague-Dawley rats were studied with a myograph. Superoxide dismutase, which scavenges superoxide anions, produced a significantly greater relaxation in the arteries from the vitamin E-deprived rats compared with the controls (P<.05). Superoxide dismutase and catalase produced results similar to superoxide dismutase alone. Pretreatment with an NO synthase inhibitor eliminated the superoxide dismutase-induced relaxation in arteries from both control and vitamin E-deprived rats. L-Arginine induced a greater relaxation in arteries of the vitamin E-deprived group (P<.05). Agonist-induced relaxation with methacholine was not altered by superoxide dismutase for either group of animals, indicating that stimulated release of NO was not influenced by superoxide anions. With the use of Western immunoblot analysis, nitrotyrosine residues were shown to be present in arteries from both the vitamin E-deprived and control rats, but the amount of nitrotyrosine observed was not different between the two groups. In summary, our data indicate that there is a greater inhibition of NO caused by superoxide anions in the vitamin E-deprived group. We speculate that in conditions of oxidative stress (reduced vitamin E levels), altered vascular function may be due to increased destruction of NO by oxygen-derived free radicals.
Hypertension 1998 Mar
PMID:Vascular function in the vitamin E-deprived rat: an interaction between nitric oxide and superoxide anions. 949 68

Administration of 100 ppm lead acetate daily for 3 months caused hypertension in Sprague-Dawley rats, with reversal by treatment with 2,3-dimercaptosuccinic acid (DMSA) (0.5% for 2 weeks). Animals from each group were infused sequentially in 30-min intervals with saline (S), L-arginine (Arg), Arg+ superoxide dismutase (SOD), S, and sodium nitroprusside (SNP). Baseline mean blood pressure (MBP) was elevated in lead-treated animals (Pb) compared to that in controls(C), returning toward normal after DMSA (105 +/- 2 mmHg, C, vs 149 +/- 2, Pb, and 124 +/- 1, DMSA, P < 0.001). Infusion of Arg caused a fall in MBP in all animals, normalizing the MBP in Pb-treated animals. SNP caused a greater fall in MBP in all groups of animals, normalizing the MBP in Pb. Measurement of urinary nitrite + nitrate (NOx) by chemiluminescence revealed at baseline a reduced level in Pb, restored to normal by DMSA (6.6 +/- 1.5 nmol/min/100 g BW, C, vs 3.3 +/- 1.7, Pb, P < 0.05, vs 5.8 +/- 2.6, DMSA, P = NS). Infusion of arginine increased urinary NOx in all groups, but to a lesser degree in Pb and DMSA. Assay of plasma malondialdehyde (MDA) by HPLC, as a measure of reactive oxygen species (ROS), was elevated at baseline in Pb, reduced by DMSA (3.6 +/- 0.4 mumol/L, Pb, vs 1.9 +/- 0.2, C, and 1.9 +/- 0.3, DMSA, P < 0.01). In the Pb group, SOD resulted in a significant fall in MDA (2.0 +/- 0.3 mumol/L, SOD, vs 3.1 +/- 0.1, Arg, P < 0.01), but no further fall in MBP or increase in urinary NOx. Thus, hypertension in lead-exposed animals is related to both diminished NO and increased ROS. The elevation in MBP can be ameliorated by additional NO through infusion of substrate arginine or by treatment with the ROS scavenger, DMSA. Lead-exposed animals show enhanced MBP sensitivity to the NO donors, Arg and SNP, but no further response to SOD, despite a reduction in MDA to normal. We speculate that lead-induced hypertension may be caused by one species of ROS which enhances vascular reactivity, and that provision of additional NO acts to scavenge the ROS and/or acts directly as a vasodilator.
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PMID:Lead-induced hypertension. II. Response to sequential infusions of L-arginine, superoxide dismutase, and nitroprusside. 951 65

Constitutive nitric oxide synthase (cNOS) with insufficient cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H4B) may generate damaging superoxide (O2-). This study was designed to determine whether cNOS-dependent generation of O2- occurs in spontaneously hypertensive rats (SHR) before the onset of hypertension. Aortas from 4-wk-old SHR and Wistar-Kyoto rats were used. cNOS was stimulated by calcium ionophore A23187. In situ measurements of nitric oxide and hydrogen peroxide by electrochemical sensors and O2- production by chemiluminescence method were performed. Isometric tension was continuously recorded. H4B by high performance liquid chromatography and [3H]citrulline assay were determined in homogenized tissue. The A23187-stimulated production of O2- and its superoxide dismutase product hydrogen peroxide were significantly higher, whereas nitric oxide release was reduced in SHR aortas, with opposite results in the presence of exogenous H4B. Furthermore, NG-monomethyl-L-arginine inhibited the generation of cNOS-dependent O2- by approximately 70%. Natural H4B levels were similar in both strains; however, equivalent cNOS activity required additional H4B in SHR. The endothelium-dependent relaxations to A23187 were significantly inhibited by catalase, and enhanced by superoxide dismutase, only in SHR; however, these enzymes had no effect in the presence of H4B. Thus, dysfunctional cNOS may be a source of O2- in prehypertensive SHR and contribute to the development of hypertension and its vascular complications.
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PMID:Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats. 952 96


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