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

The hemodynamic effects of hypertonic saline solution (HSS) resuscitation on endotoxic shock were examined in pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli (055:B5) endotoxin was infused IV at dosage of 0.1 microgram/kg of body weight for 30 minutes. Endotoxin induced large decreases in cardiac index, stroke volume, maximal rate of change of left ventricular pressure (+dP/dtmax), femoral and mesenteric arterial blood flow, glomerular filtration rate, urine production, and mean aortic pressure. Severe pulmonary arterial hypertension and increased pulmonary vascular resistance were evident at the end of endotoxin infusion. Treatment with HSS (2,400 mosm of NaCl/L, 4 ml/kg) or an equivalent sodium load of isotonic saline solution (ISS: 300 mosm of NaCl/L, 32 ml/kg) was administered 90 minutes after the end of endotoxin administration. Both solutions were infused IV over a 4- to 6-minute period. Administration of HSS induced immediate and significant (P less than 0.05) increase in stroke volume and central venous pressure, as well as significant decrease in pulmonary vascular resistance. These effects were sustained for 60 minutes, after which all variables returned toward preinfusion values. The hemodynamic response to HSS administration was suggestive of rapid plasma volume expansion and redistribution of cardiac output toward splanchnic circulation. Plasma volume expansion by HSS was minimal 60 minutes after resuscitation. Administration of ISS induced significant increase in cardiac index, stroke volume, femoral arterial blood flow, and urine production. These effects were sustained for 120 minutes, at which time, calves were euthanatized. Compared with HSS, ISS induced sustained increase in mean pulmonary arterial pressure and only a small increase in mesenteric arterial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic response of endotoxemic calves to treatment with small-volume hypertonic saline solution. 189 78

Nitric oxide is widely distributed in the body. It has an important role in the regulation of the circulation and as yet, ill-defined roles in nervous and immune systems. It is derived from L-arginine from a reaction catalysed by a constitutive intracellular enzyme, nitric oxide synthase. It is recognised as the endogenous nitrovasodilator whose action is mimicked by all exogenous nitrovasodilators. After production in the vascular endothelial cell, it diffuses to the smooth muscle cell where it activates the enzyme guanylate cyclase which leads to an increase in cyclic GMP and thence to muscle relaxation. The duration of its action is brief, a few seconds. Disorders of NO metabolism underlie many disease states including endotoxic shock in which prolonged production of nitric oxide may be induced by cytokines. Deficiencies in endogenous production may account for hypertension in various disease states including atherosclerosis and chronic renal failure. NO therapy been used experimentally to successfully treat idiopathic pulmonary hypertension and pulmonary hypertension associated with cardiac and respiratory diseases. However, the long-term benefits have yet to be studied. Administration of NO requires the use of a device to monitor the concentrations of both NO and of NO2. The latter is a noxious agent and a time-related product of the reaction between NO and O2 and is a possible contaminant of preparations of NO. Precautions must be taken to prevent contamination of the work-place atmosphere with NO and NO2. These include gas scavenging and the use of a leak-free system for spontaneous and mechanical ventilation. Using NO in its gaseous form, clinicians have at long last been provided with the means to treat pulmonary hypertension without adversely causing systemic hypotension. The therapy is most suited to short-term use in mechanically ventilated patients. Safe practical long-term NO therapy must await the development of agents which release NO from aerosol preparations.
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PMID:The role of nitric oxide (formerly endothelium-derived relaxing factor-EDRF) in vasodilatation and vasodilator therapy. 812 32

Prostacyclin, nitric oxide and tissue plasminogen activator constitute a prominent triad of endothelial mediators. Prostacyclin is responsible mainly for maintaining vascular thromboresistance against platelet clumps, inhibits proliferation of vascular smooth muscle and modulates cholesterol turnover, tissue plasminogen activator is a fibrinolytic agent and nitric oxide controls vascular tone and structure. Receptor agonists such as acetylcholine, kinins, endothelins or adenosine diphosphate evoke a coupled release of mediators from endothelial cells. Prostacyclin and nitric oxide synergize in their antiplatelet, fibrinolytic and cardioprotective, but not in their hypotensive actions. Prostacyclin, but not nitric oxide, prevents paradox thrombogenic effects of tissue plasminogen activator. Filogenetically, prostacyclin and tissue plasminogen activator are younger brothers of nitric oxide from which they take over and perfect regulatory properties in circulation. Further studies on interactions of endothelial mediators may lead to a better understanding of mechanisms of thrombosis, atherogenesis, diabetic angiopathies, endotoxic shock and arterial hypertension.
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PMID:Interactions between endothelial mediators. 853 5

Septic shock involves systemic vasodilation mediated by proinflammatory cytokines. In essential hypertension, vascular and immune dysfunctions are closely associated. The response of hypertensive animals compared with normotensive controls to endotoxin (lipopolysaccharide; LPS) challenge is not known. Age-matched (12 weeks) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to intravenous injection of 10 mg/kg LPS. Survival rate at 24 hours was markedly higher in SHR than in WKY (12 of 15 and 3 of 15, respectively; P<0.01). Survival of LPS-injected SHR was not related to their hypertension because hydralazine-treated SHR with normalized pressure had similar survival rates, and WKY made hypertensive by clipping of one renal artery showed fatality similar to that of normotensive WKY. Continuous arterial pressure and sequential plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured in LPS-treated SHR and WKY. Both the duration of the delayed hypotensive phase and the systemic release of IL-6 were much lower in SHR than WKY, whereas both acute hypotension and plasma TNF peak were equivalent. We further explored in vitro the inflammatory response and showed that LPS-activated whole blood from SHR produced less TNF and IL-6 than WKY LPS-activated whole blood. Our results indicate that SHR have a greater ability to resist endotoxic shock than WKY. This is not related to their hypertension but is associated with an attenuated inflammatory response to LPS.
Hypertension 1998 Jun
PMID:Resistance to endotoxin shock in spontaneously hypertensive rats. 962 53

There is increasing recognition that communication pathways exist between the immune system and brain, which allows bidirectional regulation of immune and brain responses to infection. The endotoxin lipopolysaccharide (LPS) has been reported to elicit release of cytokines and expression of inducible nitric oxide synthase (iNOS) in peripheral organs. Whereas LPS given systemically causes endotoxic shock, little is known about its central nervous system action, particularly the induction of iNOS. Nitric oxide (NO) and glutamate in the nucleus tractus solitarii (NTS) are important mediators of central cardiovascular regulation. We have previously demonstrated that intravenous injections of LPS increased the NO precursor L-arginine-induced depressor effect in the NTS. The present study investigated further the effects of LPS on the release of NO and glutamate in the NTS and the expression of c-fos, an immediate early response gene product, in neural substrates for central cardiovascular control. In vivo microdialysis coupled with chemiluminescence and electrochemical detection techniques were used to measure extracellular levels of NO and glutamate in the rat NTS. Immunohistochemistry was used for the examination of c-fos protein expression. We found that intravenous infusion of LPS (10 mg/kg) produced a biphasic depressor effect, with an early, sharp hypotension that partially recovered in 15 minutes and a secondary, more prolonged hypotension. In the NTS, a progressive increase of extracellular glutamate and NO levels occurred 3 and 4 hours after LPS was given, respectively. The effects of LPS on the induction of delayed hypotension and NO formation in the NTS were abolished by pretreatment with the iNOS inhibitor aminoguanidine. Finally, c-fos protein expression in the NTS and related structures for cardiovascular regulation was observed after LPS challenge. Taken together, these data suggest that an endotoxin given systemically can elicit delayed increases of glutamate release and iNOS-dependent NO production in the NTS and activate the central neural pathway for modulating cardiovascular function.
Hypertension 1999 May
PMID:Systemic administration of lipopolysaccharide induces release of nitric oxide and glutamate and c-fos expression in the nucleus tractus solitarii of rats. 1033 15

We evaluated the role of endothelin-1 (ET-1) and the involvement of nitric oxide in cardiovascular and respiratory dysfunction, during endotoxic shock, in 18 anaesthetised, mechanically ventilated pigs, divided into three groups. Group 1 was i.v. infused with LPS (20 microg/Kg/h for 240 min). Group 2 was pre-treated with bosentan, a dual inhibitor of ET-1 receptors, and at 180 min of endotoxic shock, L-NAME (N(G)-nitro-L-arginine methyl ester, 10 mg/Kg), a non-selective inhibitor of NO synthases, was i.v. administered. Group 3 was infused with LPS and L-NAME was administered similarly to group 2. Results show that LPS caused systemic hypotension, pulmonary biphasic hypertension, decrease in compliance (C(rs)) and increase in resistance (R(max,rs)) of respiratory system. Bosentan completely abolished the pulmonary hypertension and the changes in C(rs)and R(max,rs). L-NAME does not affect the LPS-dependent changes in respiratory mechanics, but it worsens the cardiovascular effects, causing death of pigs. Pre-treatment with bosentan prevents this deleterious effect. Our study demonstrates that the LPS-dependent respiratory effects are mediated by ET-1, which, probably causing pulmonary oedema, is responsible for the decrease in C(rs)and the increase of R(max,rs).
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PMID:Improvement of respiratory function by bosentan during endotoxic shock in the pig. 1154 27

To explore the mechanism underlying cholecystokinin octapeptide (CCK-8) induced attenuation in pulmonary arterial hypertension (PAH) in endotoxic shock (ES), the effect of CCK-8 on the changes in rabbit pulmonary arterial reactivity induced by tumor necrosis factor-alpha (TNF-alpha) was observed with isolated arterial ring technique and by examination of nitric oxide synthase (NOS). The contractile response to 10(-6) mol/L phenylephrine (PE) and the endothelium dependent relaxation response to 10(-6) mol/L acetylcholine (ACh) were not affected by TNF-alpha (4000 U/ml) after incubation for 2 h; the relaxation response was decreased significantly when the incubation was prolonged to 7 or 14 h, which, however, could be reversed by a concomitant exposure to CCK-8 (0.5 microgram/ml), but the incubation of pulmonary arterial rings with CCK-8 (0.5 microgram/ml) alone did not bring out any contractile responses. The endothelium dependent relaxation response to 10(-6) mol/L ACh was restored by L arginine in the TNF-alpha group which had been incubated for 7 h, but was not affected by AG in each group, while the contractile response to 10(-6) mol/L PE increased significantly in the TNF-alpha group. The relaxant response to 10(-6) mol/L ACh changed into a contractile response after preincubation with L-NNA in each group, while the contraction response to 10(-6) mol/L PE increased significantly. The NOS activity increased in the TNF-alpha and the TNF alpha+CCK-8 groups, while no significant difference was observed between the vehicle and the CCK-8 groups. These results suggest that CCK-8 prevents TNF-alpha induced impairment in endothelium dependent relaxation response, and the effects of both CCK-8 and TNF-alpha are related to NO.
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PMID:[Role of nitric oxide in cholecystokinin octapeptide alleviation of tumor necrosis factor alpha induced changes in rabbit pulmonary arterial reactivity]. 1193 Feb 30

To explore the mechanism underlying cholecystokinin-octapeptide (CCK-8) induced attenuation of pulmonary arterial hypertension (PAH) in endotoxic shock, the effects of CCK-8 on the changes in rabbit pulmonary arterial reactivity induced by tumor necrosis factor-alpha (TNF-alpha) were observed with the isolated arterial ring technique, and the ultrastructure of pulmonary arterial endothelium was observed under a scanning electron microscope. The contractile response to -adrenoceptor agonist phenylephrine (PE), the endothelium-dependent relaxation response to acetylcholine (ACh) and the endothelium-independent relaxation response to sodium nitroprusside (SNP) were not affected by TNF-alpha (4000 U/ml) after incubation for 2 h, while, if the incubation time was prolonged to 7 or 14 h, the relaxation response of pulmonary artery to ACh was depressed significantly, which, however, could be reversed by concomitant exposure to CCK-8 (0.5 microgram/ml). Incubation of pulmonary artery with CCK-8 (0.5 microgram/ml) alone did not bring out any contractile responses. Moreover, CCK-8 (0.5 microgram/ml) alleviated the ultrastructural lesions induced by TNF-alpha (4000 U/ml). These results suggest that CCK could protect pulmonary arterial endothelium against the detrimental effects by TNF-alpha.
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PMID:[Cholecystokinin-octapeptide alleviates tumor necrosis factor-alpha induced changes in rabbit pulmonary arterial reactivity and injuries of endothelium in vitro]. 1194 16

Heme plays a significant pathogenic role in several diseases involving the kidney. The cellular content of heme, derived either from the delivery of filtered heme proteins such as hemoglobin and myoglobin, or from the breakdown of ubiquitous intracellular heme proteins, is regulated via the heme oxygenase enzyme system. Heme oxygenases catalyze the rate-limiting step in heme degradation, resulting in the formation of iron, carbon monoxide, and biliverdin, which is subsequently converted to bilirubin by biliverdin reductase. Recent attention has focused on the biological effects of product(s) of this enzymatic reaction, which have important antioxidant, anti-inflammatory, and cytoprotective functions. Three isoforms of heme oxygenase (HO) enzyme have been described: an inducible isoform, HO-1, and two constitutively expressed isoforms, HO-2 and HO-3. Induction of HO-1 occurs as an adaptive and beneficial response to several injurious stimuli, and has been implicated in many clinically relevant disease states including atherosclerosis, transplant rejection, endotoxic shock, hypertension, acute lung injury, acute renal injury, as well as others. This review will focus predominantly on the role of HO-1 in the kidney.
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PMID:Heme oxygenase and the kidney. 1204 70

The inhibition of nitric oxide (NO) synthesis by chronic administration of NG-nitro-l-arginine methyl ester (l-NAME) in rats is responsible for systemic hypertension. However, the mechanisms involved in this hypertension remain unclear. The effects of chronic l-NAME on kidney and blood NO production were studied in rats in a state of endotoxic shock due to lipopolysaccharide (LPS). A nitric oxide spin trapping technique using electron spin resonance (ESR) spectroscopy has been used to identify and measure the production of NO in the kidney. This method is based on the trapping of nitric oxide by a metal-chelator complex consisting of N-methyl-d-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+) forming a water-soluble NO-FeMGD complex detected by ESR. After LPS injection (14 mg/kg, IV, 6 h before the sacrifice) to rats pretreated with l-NAME (10 mg/kg/d over 14 days), the NO-FeMGD complex was evaluated in the kidney (arbitrary units [AU]/g of kidney) and the density of polynuclear neutrophils was counted by light microscopy. Chronic inhibition of NO synthase by l-NAME, a nonspecific inhibitor, was responsible for a decrease of the NO-FeMGD complex levels in the kidney (24.9 +/- 1.6 AU versus 13.8 +/- 1.3 AU). LPS administration was responsible for a large increase in both NO-FeMGD complex and neutrophil levels in the kidney of normotensive rats (332.6 +/- 12.8 AU versus 24.9 +/- 1.6 AU for NO-FeMGD complex and 1.36 +/- 0.41 versus 0.11 +/- 0.03 for neutrophils). Conversely, LPS administration in hypertensive, l-NAME-pretreated rats was linked to a smaller increase in the NO-FeMGD complex (85.1 +/- 7.9 AU versus 332.6 +/- 12.8 AU) and a larger increase in glomerular neutrophils (2.48 +/- 0.36 versus 1.36 +/- 0.41) compared with normotensive rats. These results are in agreement with a direct implication of NO during LPS-and l-NAME-induced kidney injuries.
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PMID:Intrarenal detection of nitric oxide using electron spin resonance spectroscopy in hypertensive lipopolysaccharide-treated rats. 1207 72


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