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

The amounts of tissue factor (TF) expressed by brain microvascular endothelial cells (BMECs) from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were compared after stimulating the cells with different doses of lipopolysaccharide (LPS), thrombin, phorbol myristic acid (PMA), Ca(2+)-ionophore (A23187), or tumor necrosis factor (TNF) and interleukin-1 (IL-1). Treatment of cultured BMECs from WKY and SHR with all of these factors dose-dependently increased their total amount of TF; no substantive differences in the levels of enhanced TF expression were observed between WKY and SHR BMECs. We conclude that stimulated endothelium from rats with hypertension, a major stroke risk factor, is not hyperresponsive with respect to TF expression when compared to normotensive controls.
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PMID:Comparison of stimulated tissue factor expression by brain microvascular endothelial cells from normotensive (WKY) and hypertensive (SHR) rats. 147 6

Immune dysfunction has been reported in spontaneously hypertensive rats (SHR), particularly in mature animals with established hypertension. The current study examined the time course of development of immune dysfunction and defined its cellular basis in male SHR and control normotensive Wistar-Kyoto rats (WKY). Mitogen-induced proliferative responses in lymphoid cells obtained from induced proliferative responses in lymphoid cells obtained from SHR thymus and spleen before (age 4 wk) and during the development of (ages 8 and 12 wk) hypertension and in age-matched normotensive WKY were monitored. A 50% reduction in concanavalin A (Con A)-induced proliferative responses was seen in SHR thymocytes compared with those of WKY at 12 wk only, suggesting differences in immature T-cell populations. Con A-induced T-cell proliferative responses in splenocytes also differed between strains: greatest (as much as 8-fold) decreases were found in 12-wk-old SHR. Similar findings were obtained in splenocytes stimulated with lipopolysaccharide (LPS), indicating differences in B-cell function. Mononuclear cells depleted of their adherent cell population were prepared from SHR and WKY at 12+ wk of age and assayed for their proliferative responses to LPS and Con A. The remaining nonadherent mononuclear cells of SHR had proliferative responses equal to or greater than those of WKY. Further, when SHR splenic mononuclear cells were allowed to adhere to plastic, and the adherent fraction was co-cultured with either SHR G-10 nonadherent or unfractionated SHR splenic mononuclear cells, proliferative responses were suppressed by as much as 88%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spontaneously hypertensive rat: lymphoid depression is age dependent and mediated via a mononuclear cell subpopulation. 173 28

1. The effects on blood pressure and on pressor responses to noradrenaline (NA), of NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), inhibitors of the L-arginine/nitric oxide pathway, were investigated in anaesthetized rats receiving an infusion of bacterial endotoxin (E. coli lipopolysaccharide, LPS). 2. Infusion of LPS (10 mg kg-1 h-1) for 50 min had no effect on mean arterial blood pressure (MABP) but induced a reduction in responsiveness to noradrenaline (100 ng-1 micrograms kg-1). L-NMMA (30 mg kg-1), but not D-NMMA, caused an increase in MABP of approximately 30 mmHg and restored responses to NA. This effect was reversed by L- but not D-arginine (100 mg kg-1). 3. In LPS-treated rats, blood pressure responses to NA were only marginally increased by the cyclooxygenase inhibitor, indomethacin (5 mg kg-1). L-NAME (1 mg kg-1) caused a similar increase in MABP and restored pressor responses to NA both in the presence and absence of indomethacin. 4. Co-infusion of vasopressin (100 ng kg-1, for 10 min) with LPS (10 mg kg-1 h-1) in order to reproduce the hypertensive effect of L-NMMA and L-NAME increased pressor responsiveness to 100 and 300 ng kg-1 NA but not to 1 microgram kg-1 NA. 5. Infusion of sodium nitroprusside (30 micrograms kg-1 min-1) decreased responsiveness to NA even when the hypotension was corrected by co-infusion of vasopressin (50 ng kg-1 min-1). 6. These results demonstrate that the restoration of vascular responsiveness to NA in LPS-treated anaesthetized rats by inhibitors of the L-arginine/nitric oxide pathway is stereospecific and reversible. Furthermore, the experiments involving indomethacin suggest that although cyclo-oxygenase products of arachidonic acid may contribute to the development of LPS-induced hyporeactivity, the effect of L-NAME is unlikely to involve inhibition of the cyclo-oxygenase pathway. Comparison of NA responsiveness during vasopressin and L-NMMA/L-NAME-induced hypertension shows that increasing the blood pressure may modify LPS-induced hyporeactivity, but cannot account for the complete restoration of responses to NA by L-NMMA and L-NAME. These observations suggest that activation of nitric oxide formation from L-arginine makes a direct contribution to the production of vascular hyporeactivity by LPS in vivo.
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PMID:The effect of inhibitors of the L-arginine/nitric oxide pathway on endotoxin-induced loss of vascular responsiveness in anaesthetized rats. 190 34

Rats produced more TNF activity in cerebrospinal fluid (CSF) than in blood after intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). After intravenous (i.v.) LPS, blood TNF levels exceeded CSF levels. Thus, brain cells appear to produce TNF in response to LPS. Rats with the stroke-risk factors hypertension or combined hypertension and genetic stroke-proneness produce more TNF in response to a provocative dose of LPS i.v. than control animals free of these risk factors. The possible relevance to stroke vulnerability is discussed.
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PMID:Lipopolysaccharide-induced production of tumor necrosis factor activity in rats with and without risk factors for stroke. 202 11

We infused recombinant human tumor necrosis factor alpha (rhTNF alpha), lymphotoxin (rhLT), and Escherichia coli 0111:B4 lipopolysaccharide (LPS) into anesthetized sheep with a lung lymph fistula to compare their effects on systemic and pulmonary hemodynamics, lung lymph dynamics, and eicosanoid release. rhTNF alpha (25-150 micrograms/kg, n = 6 sheep), but not rhLT (25 micrograms/kg, n = 3), rapidly increased lung lymph and plasma levels of 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) and caused profound systemic vasodilation and hypotension. Meclofenamate pretreatment (10 mg/kg) of three other sheep given 25 micrograms/kg rhTNF alpha prevented the increase of lymph and plasma 6-k-PGF1 alpha levels, systemic vasodilation, and the early (less than 2 hrs) but not the late (4-6 hours) hypotension caused by rhTNF alpha. LPS (1 micrograms/kg, n = 11) induced a briefer increase of lymph 6-k-PGF1 alpha levels than did rhTNF alpha while plasma 6-k-PGF1 alpha levels did not increase. LPS induced more gradual hypotension than did rhTNF alpha but did not cause systemic vasodilation. LPS and rhTNF alpha, but not rhLT, increased lymph thromboxane B2 (TXB2) levels during the first hour of study, whereas only LPS acutely increased plasma TXB2 levels. LPS caused acute pulmonary vasoconstriction and greater acute pulmonary artery hypertension than did either rhTNF alpha or rhLT. Whereas LPS-treated sheep required less fluid transfusion than rhTNF alpha-treated sheep to maintain mean systemic arterial pressure greater than 50 mm Hg, LPS infusion caused a greater increase of lung lymph protein clearance. rhTNF alpha caused minimal alterations of lung microvascular permeability. We conclude that eicosanoid mediators contribute importantly to differences of systemic and pulmonary hemodynamics caused by these agents in sheep. rhTNF alpha cannot account for all of the LPS-induced hemodynamic, lung lymph, and eicosanoid responses in sheep.
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PMID:Effects of recombinant human tumor necrosis factor alpha, lymphotoxin, and Escherichia coli lipopolysaccharide on hemodynamics, lung microvascular permeability, and eicosanoid synthesis in anesthetized sheep. 266 72

Lipid X (2,3-diacylglucosamine-1-phosphate) is a novel monosaccharide precursor of lipid A that has some of the physiologic activities of endotoxin but little toxicity. To determine whether lipid X would interfere with the toxic effects of endotoxin, we pretreated sheep with either 100 or 200 micrograms of lipid X per kg of body weight and then challenged them with a potentially fatal dose of Escherichia coli endotoxin (20 micrograms/kg). Twenty-one sheep underwent pulmonary artery catheterization and were monitored for changes in pulmonary artery pressure, temperature, pH, partial O2 pressure, partial CO2 pressure, blood pressure, and cell counts over 7 h. Overall mortality for control animals was 37% versus 5.3% for pretreated animals. None of the 13 animals pretreated with 100 micrograms of lipid X per kg died. These differences in survival were significant (P less than 0.05). Animals pretreated with 100 micrograms of lipid X per kg had significantly lower pulmonary artery pressure during both phases 1 and 2 of endotoxin-induced pulmonary artery hypertension. A higher dose of lipid X, 200 micrograms/kg, produced pulmonary hypertension. Perhaps because lipid X is a subunit of lipid A, lipid X shows a partial pyrogenic effect while also decreasing the pyrogenic activity of complete lipopolysaccharide (LPS). Lipid X did not prevent endotoxin-induced neutropenia or moderate hypotension in response to LPS. Lipid X is a potential prototype compound for a new type of chemotherapy directed at blocking the harmful effects of LPS during bacterial septicemia.
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PMID:Lipid X ameliorates pulmonary hypertension and protects sheep from death due to endotoxin. 330 7

We studied the effects of superoxide dismutase (SOD), an enzyme that converts superoxide into peroxide, on the cardiopulmonary response to endotoxin in sheep. Sheep (n = 18) were prepared for chronic measurement of cardiopulmonary variables, including lung lymph flow, by surgically implanting catheters under halothane anesthesia. Nine of the animals were studied before and after the administration of endotoxin (0.75 microgram/kg) with and without SOD. An additional nine animals received SOD without the lipopolysaccharide. Endotoxin produced an increase in lung lymph flow that was initially associated with a marked pulmonary arterial (PA) hypertension and reduced lymph-to-plasma protein ratio (L/P). The lymph flow remained elevated later in the response, but there was only a mild increase in PA pressure, and the L/P was normal. There was also a fall in blood neutrophils and in cardiac index. SOD increased this secondary elevation in lung lymph flow, and the corresponding L/P was greater than the preendotoxin value. The fall in neutrophil count, cardiac output, and the elevation in PA pressure seen with endotoxin were not affected by SOD. When administered in the absence of endotoxin, SOD produced no perceptible change in the cardiopulmonary and lymph values. We conclude that peroxide, hydroxyl ion, and/or other free radicals formed by the action of SOD must be responsible for a portion of the endotoxin response rather than superoxide itself.
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PMID:Potentiation of lung vascular response to endotoxin by superoxide dismutase. 398 Mar 70

Nitric oxide is a potent endogenous vasodilator that regulates arterial tone. A family of nitric oxide synthases uses L-arginine and L-homoarginine stereospecifically as substrates for nitric oxide production in vivo. By preventing expression of inducible but not constitutive nitric oxide synthases, glucocorticoids differentiate which enzyme in this family is the predominant source of nitric oxide generation in a given situation. We proposed that defective production of nitric oxide produces salt-sensitive hypertension in the Dahl/Rapp rat. Plasma concentrations of L-arginine, citrulline, and ornithine of salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats on 8% sodium chloride chow for 1 week did not differ. However, intravenous infusion of L-arginine and L-homoarginine, but not D-arginine, increased urinary excretion of nitrate, the degradation product of nitric oxide, and simultaneously lowered blood pressure in hypertensive SS/Jr rats. Oral L-arginine also prevented development of hypertension and increased urinary excretion of cyclic GMP and nitrate in these rats. Dexamethasone, in a dose that prevented hypotension from parenteral injection of lipopolysaccharide, completely prevented the increase in excretion of cyclic GMP and nitrate, and hypertension resulted despite concomitant treatment with L-arginine. These studies supported an important role of dexamethasone-suppressible nitric oxide synthesis in the prevention of salt-sensitive hypertension in the Dahl/Rapp rat.
Hypertension 1993 Dec
PMID:Role of nitric oxide synthesis in salt-sensitive hypertension in Dahl/Rapp rats. 750 51

Angiotensinogen has been assumed to be an acute-phase protein, because some forms of acute inflammation, eg, the injection of lipopolysaccharide or cellite or partial hepatectomy, increased the hepatic synthesis of angiotensinogen. In addition, the well-characterized nephrectomy-induced stimulation of angiotensinogen was thought to represent an acute-phase reaction. To evaluate this hypothesis, we examined changes in angiotensinogen secretion by the isolated perfused rat liver after the systemic administration of turpentine or lipopolysaccharide as well as in response to nephrectomy or sham nephrectomy. Comparison was made with the secretion of two typical acute-phase proteins, alpha 1-acid glycoprotein and alpha 2-macroglobulin, and with the secretion of the negative acute-phase protein albumin. All forms of experimental surgery stimulated the secretion of both control acute-phase proteins several-fold. In contrast, the response of angiotensinogen was not uniform; lipopolysaccharide and bilateral nephrectomy stimulated secretion twofold to threefold, sham nephrectomy had no effect, and turpentine decreased the secretion to 30% of the control level. A similar inhomogeneity was found in an additional experiment performed to analyze the direct effects of interleukin-1 or interleukin-6 on the secretion of angiotensinogen by freshly isolated hepatocytes. Interleukin-6 increased but interleukin-1 decreased the mRNA and secretion of angiotensinogen, whereas both cytokines increased the secretion of both acute-phase proteins. Because of this nonuniform behavior of angiotensinogen, it is premature to classify angiotensinogen as an acute-phase protein until a specific function for angiotensinogen during acute inflammation is known.
Hypertension 1994 Jan
PMID:Angiotensinogen: an acute-phase protein? 750 96

Three isozymes of nitric oxide (NO) synthase (EC 1.14.13.39) have been identified and the cDNAs for these enzymes isolated. In humans, isozymes I (in neuronal and epithelial cells), II (in cytokine-induced cells), and III (in endothelial cells) are encoded for by three different genes located on chromosomes 12, 17, and 7, respectively. The deduced amino acid sequences of the human isozymes show less than 59% identity. Across species, amino acid sequences for each isoform are well conserved (> 90% for isoforms I and III, > 80% for isoform II). All isoforms use L-arginine and molecular oxygen as substrates and require the cofactors NADPH, 6(R)-5,6,7,8-tetrahydrobiopterin, flavin adenine dinucleotide, and flavin mononucleotide. They all bind calmodulin and contain heme. Isoform I is constitutively present in central and peripheral neuronal cells and certain epithelial cells. Its activity is regulated by Ca2+ and calmodulin. Its functions include long-term regulation of synaptic transmission in the central nervous system, central regulation of blood pressure, smooth muscle relaxation, and vasodilation via peripheral nitrergic nerves. It has also been implicated in neuronal death in cerebrovascular stroke. Expression of isoform II of NO synthase can be induced with lipopolysaccharide and cytokines in a multitude of different cells. Based on sequencing data there is no evidence for more than one inducible isozyme at this time. NO synthase II is not regulated by Ca2+; it produces large amounts of NO that has cytostatic effects on parasitic target cells by inhibiting iron-containing enzymes and causing DNA fragmentation. Induced NO synthase II is involved in the pathophysiology of autoimmune diseases and septic shock. Isoform III of NO synthase has been found mostly in endothelial cells. It is constitutively expressed, but expression can be enhanced, eg, by shear stress. Its activity is regulated by Ca2+ and calmodulin. NO from endothelial cells keeps blood vessels dilated, prevents the adhesion of platelets and white cells, and probably inhibits vascular smooth muscle proliferation.
Hypertension 1994 Jun
PMID:Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. 751 53


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