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

Ciglitazone is the prototype of the thiazolidinedione class of compounds currently being developed for the treatment of insulin resistance and non-insulin-dependent diabetes. The effects of thiazolidinediones on blood pressure and cell calcium metabolism are not well defined. In the obese Zucker rat, a widely studied model of insulin resistance associated with mild hypertension, we investigated the effects of ciglitazone on plasma insulin levels and mean arterial pressure. We also evaluated the effects of ciglitazone on the changes in cytosolic calcium induced by platelet-derived growth factor in A172 human glioblastoma cells and rat A10 vascular smooth muscle cells. Oral administration of ciglitazone, approximately 45 mg/kg per day for 4 weeks, induced significant reductions in plasma insulin levels (p < 0.001) and blood pressure (p < 0.05). Ciglitazone was also found to significantly attenuate the capacity of platelet-derived growth factor BB homodimer to induce sustained increases in intracellular free calcium. These findings suggest that thiazolidinediones may offer a novel pharmacological approach to the treatment of hypertension, and raise the possibility that these compounds may affect blood pressure not only by affecting insulin metabolism but also by modifying the cell calcium response to pressor agents, growth factors, or both.
Hypertension 1993 Jun
PMID:Effects of ciglitazone on blood pressure and intracellular calcium metabolism. 850 86

Imbalance of zinc and copper status has been hypothesized in human hypertension. A case-control study was carried out to elucidate the possible relationship between zinc and copper status and essential hypertension. Thirty-one subjects affected by mild stable hypertension, pharmacologically untreated, were investigated together with 31 normotensive controls individually matched for sex, age, and smoking habits. Zinc and copper in serum and urine wee measured, and serum activities of alkaline phosphatase (AP), lactic dehydrogenase (LDH), copper-zinc superoxide dismutase (Cu-Zn SOD), lysyl oxidase (LOX), and monoamine oxidase (MAO) were evaluated. No significant difference in serum and urine zinc and copper content as far as in serum activity of zinc (AP and LDH) or copper (Cu-Zn SOD, LOX, and MAO)-dependent enzymes was found between hypertensives and normotensives. Positive relationships were found in normotensives between serum and urine levels of zinc (r = 0.577; p = 0.001) and copper (r = 0.394; p = 0.028), and between serum copper and Cu-Zn SOD (r = 0.534; p = 0.002). In normotensives, diastolic blood pressure and serum zinc were positively related (r = 0.370; p = 0.041). In hypertensives, inverse correlations were observed between diastolic blood pressure and AP (r = -0.498; p = 0.004) and Cu-Zn SOD (r = 0.452; p = 0.011), and between systolic blood pressure and LOX (r = -0.385; p = 0.033). Diastolic blood pressure was related to LDH inversely in hypertensives (r = -0.357; p = 0.049) and positively in normotensives (r = 0.457; p = 0.010). In normotensives, diastolic blood pressure was inversely related with MAO (r = -0.360; p = 0.046). These findings support the hypothesis that an imbalance of zinc and copper status might be involved in human hypertension.
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PMID:Zinc, copper, and zinc- or copper-dependent enzymes in human hypertension. 856 90

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

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

HBP-1a(17) is representative of a group of plant bZIP-type transcription factors which includes HBP-1a proteins and G-box-binding factors. We found kinase activity in wheat nuclear extract that phosphorylated HBP-1a(17). Experiments using recombinant HBP-1a(17) derivatives as substrates revealed that all three of the Ser residues in the basic region, Ser-261, Ser-265, and Ser-269, were phosphorylated in a Ca(2+)-stimulated manner. DNA-binding analysis of mutants with a Ser-to-Glu change, prepared to mimic the phosphorylated proteins, indicated that introduction of a negative charge at position 265 or 269 prevents HBP-1a(17) from binding DNA not only in the homodimer of mutants but also in heterodimers with a wild-type protein. It is therefore suggested that the phosphorylation regulates the function of HBP-1a(17) at least at the level of DNA binding. Since Ser-265 and Ser-269 are highly conserved among the plant bZIP-type factors known to date, a common Ca(2+)-mediated regulatory mechanism may exert an effect on the bZIP-type factors through phosphorylation of these conserved Ser residues.
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PMID:Conserved Ser residues in the basic region of the bZIP-type transcription factor HBP-1a(17): importance in DNA binding and possible targets for phosphorylation. 948 68

Several DNA-binding proteins with conserved basic region/leucine zipper domains (bZIP) have been isolated from parsley. They all recognise defined ACGT-containing elements (ACEs), including ACE(PcCHSII) in the Light Regulatory Unit LRU1 of the CHS promoter which confers light responsiveness. A new member of this Common Plant Regulatory Factor (CPRF) family, designated CPRF4a, has been cloned, which displays sequence similarity to HBP-1a from wheat, as well as to other plant bZIP proteins. CPRF4a specifically binds as a homodimer to ACE(PcCHSII) and forms heterodimers with CPRF1 but not with CPRF2. In adult parsley plants, CPRF2 and CPRF4a mRNAs are found in all tissues and organs in which the chalcone synthase gene CHS is expressed. In protoplasts from suspension cultured cells, UV irradiation (290-350 nm) did not cause an increase in levels of CPRF1, CPRF2, or CPRF4a mRNA, whereas the corresponding CPRF proteins accumulated within 15 min of light treatment. Furthermore, the rapid light-mediated increase of CPRF proteins was insensitive to transcriptional inhibitors, suggesting that a post-transcriptional mechanism controls CPRF accumulation. CPRFs as well as Arabidopsis thaliana G-box binding factors (GBFs) are selectively transported from the cytosol into the nucleus, as shown in an in vitro nuclear transport system prepared from evacuolated parsley protoplasts, indicating that cytosolic compounds are involved in regulated nuclear targeting of plant bZIP factors.
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PMID:CPRF4a, a novel plant bZIP protein of the CPRF family: comparative analyses of light-dependent expression, post-transcriptional regulation, nuclear import and heterodimerisation. 960 82

The concentration of copper (Cu) and zinc (Zn) in hair and urine were studied in young nonpregnant healthy women whose both parents were diagnosed for noninsulin-dependent diabetes mellitus (NIDDM descendants) and were compared with those of young healthy nonpregnant females with no family history of NIDDM or hypertension (non-NIDDM descendants) and NIDDM patients. The concentration of Zn in hair in NIDDM descendants was significantly higher than that of non-NIDDM descendants (p < 0.001) and insignificantly higher than that of NIDDM patients. The hair Cu concentrations in NIDDM descendant and patients were significantly lower than that of non-NIDDM descendants (p < 0.001). Hyperzincuria was detected in some NIDDM patients and hypocuperuria in all NIDDM descendants and patients. The data suggest that the young healthy NIDDM descendants possess high-Zn and low-Cu reserves in their bodies, and the observed perturbation appears to be associated with Cu-Zn antagonism.
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PMID:Assessment of copper and zinc status in hair and urine of young women descendants of NIDDM parents. 967 87

Recent evidence suggests that oxidative mechanisms may be involved in vascular smooth muscle cell (VSMC) hypertrophy. We previously showed that angiotensin II (Ang II) increases superoxide production by activating an NADH/NADPH oxidase, which contributes to hypertrophy. In this study, we determined whether Ang II stimulation of this oxidase results in H2O2 production by studying the effects of Ang II on intracellular H2O2 generation, intracellular superoxide dismutase and catalase activity, and hypertrophy. Ang II (100 nmol/L) significantly increased intracellular H2O2 levels at 4 hours. Neither superoxide dismutase activity nor catalase activity was affected by Ang II; the SOD present in VSMCs is sufficient to metabolize Ang II-stimulated superoxide to H2O2, which accumulates more rapidly than it is degraded by catalase. This increase in H2O2 was inhibited by extracellular catalase, diphenylene iodonium, an inhibitor of the NADH/NADPH oxidase, and the AT1 receptor blocker losartan. In VSMCs stably transfected with antisense p22phox, a critical component of the NADH/NADPH oxidase in which oxidase activity was markedly reduced, Ang II-induced production of H2O2 was almost completely inhibited, confirming that the source of Ang II-induced H2O2 was the NADH/NADPH oxidase. Using a novel cell line that stably overexpresses catalase, we showed that this increased H2O2 is a critical step in VSMC hypertrophy, a hallmark of many vascular diseases. Inhibition of intracellular superoxide dismutase by diethylthiocarbamate (1 mmol/L) also resulted in attenuation of Ang II-induced hypertrophy (62+/-2% inhibition). These data indicate that AT1 receptor-mediated production of superoxide generated by the NADH/NADPH oxidase is followed by an increase in intracellular H2O2, suggesting a specific role for these oxygen species and scavenging systems in modifying the intracellular redox state in vascular growth.
Hypertension 1998 Sep
PMID:Role of NADH/NADPH oxidase-derived H2O2 in angiotensin II-induced vascular hypertrophy. 974 Jun 15

The present study analyses the influence of hypertension and endothelium on the effect induced by hydrogen peroxide (H2O2) on basal tone in aortic segments from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) of 6-month-old, as well as the possible mechanisms involved. Single (1 mM) or cumulative (100 nM-10 mM) concentrations of H2O2 produced a transient contraction or a concentration-dependent increase of basal tone, respectively, in segments from WKY and SHR. In both cases, the contractions were higher in intact segments from hypertensive than from normotensive rats, and increased by endothelium removal in both strains. Catalase (1000 u ml(-1), a H2O2 scavenger) abolished the contraction elicited by 1 mM H2O2 in both strains. Superoxide dismutase (SOD, 150 u ml(-1)) and dimethylsulphoxide (DMSO, 7 mM), scavengers of superoxide anions and hydroxyl radicals, respectively, did not alter H2O2-induced contractions in intact segments from both strains. However, L-NG-nitroarginine methyl ester (L-NAME, 100 microM, a nitric oxide synthase inhibitor) increased the response to H2O2 in normotensive rats, although the increase was less than that produced by endothelium removal. Incubation of segments with 1 mM H2O2 for 15 min and subsequent washout reduced the contractile responses induced by 75 mM KCl in intact segments from SHR and in endothelium-denuded segments from both strains; this effect being prevented by catalase (1000 u ml(-1)). Indomethacin (10 microM, a cyclo-oxygenase inhibitor) and SQ 29,548 (10 microM, a prostaglandin H2/thromboxane A2 receptor antagonist) practically abolished the contractions elicited by H2O2 in normotensive and hypertensive rats. We conclude that: (1) the oxidant stress induced by H2O2 produces contractions mediated by generation of a product of the cyclo-oxygenase pathway, prostaglandin H2 or more probably thromboxane A2, in normotensive and hypertensive rats; (2) oxygen-derived free radicals are not involved in the effect of H2O2; (3) in normotensive rats, endothelium protects against H2O2-mediated injury to contractile machinery, determined by the impairment of KCl-induced contractions; and (4) endothelial nitric oxide has a protective role on the contractile effect induced by H2O2, that is lost in hypertension.
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PMID:Contractile responses elicited by hydrogen peroxide in aorta from normotensive and hypertensive rats. Endothelial modulation and mechanism involved. 986 64

Angiotensin II and hypertension increase vascular oxidant stress. We examined how these might affect expression of the extracellular superoxide dismutase (ecSOD), a major form of vascular SOD. In mice, angiotensin II infusion (1.1 mg/kg for 7 days) increased systolic blood pressure from 107+/-3 to 152+/-9 mm Hg and caused a 3-fold increase in ecSOD, but there was no change in the cytosolic Cu/Zn SOD protein, as determined by Western blot analysis. This was associated with a similar increase in ecSOD mRNA as assessed by RNase protection assay and was prevented by losartan. Induction of ecSOD by angiotensin II was not due to hypertension alone, because hypertension caused by norepinephrine (5.6 mg. kg-1. d-1) had no effect on ecSOD. Similarly, exposure of mouse aortas to angiotensin II (100 nmol/L) in organoid culture increased ecSOD by approximately 2-fold. In the organoid culture, angiotensin II-induced upregulation of ecSOD was prevented by losartan (10 micromol/L) and PD985059 (30 micromol/L), a specific inhibitor of p42/44 MAP kinase kinase. Angiotensin II activates the NADH/NADPH oxidase; however, diphenyleneiodonium chloride (10 micromol/L), an inhibitor of this oxidase, did not prevent p42/44 MAP kinase phosphorylation or ecSOD induction by angiotensin II. Finally, in human aortic smooth muscle cells, angiotensin II moderately increased transcriptional rate (as assessed by nuclear run-on analysis) but markedly increased ecSOD mRNA stability. Thus, angiotensin II increases ecSOD expression independent of hypertension, and this increase involves both an increase in ecSOD transcription and stabilization of ecSOD mRNA. This effect of angiotensin II on ecSOD expression may modulate the oxidative state of the vessel wall in pathological processes in which the renin-angiotensin system is activated.
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PMID:Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. 1040 Sep 7


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