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

Nitric oxide (NO) synthesis is induced in glomeruli in glomerulonephritis; its role in the pathogenesis of glomerular injury is unknown. Interpretation of its role using the currently available analogues of L-arginine as in vivo inhibitors of NO is complicated by their lack of specificity for inducible NO synthase (iNOS). As NO synthesis by iNOS depends on extracellular L-arginine, we have here examined effects of L-arginine depletion on glomerular NO synthesis and the course of accelerated nephrotoxic nephritis (NTN). Arginase, which converts L-arginine to urea and L-ornithine, was used to achieve L-arginine depletion. A single dose of i.v. arginase produced complete depletion of plasma arginine for four hours. Two forms of NTN were induced in preimmunised rats by nephrotoxic globulin: (1) the systemic form of the model by intravenous nephrotoxic globulin; or (2) the unilateral form of model by left kidney perfusion with nephrotoxic globulin, which avoids the complications of systemic administration of nephrotoxic globulin. Arginase reduced plasma arginine levels and the synthesis of nitrite (the stable end-product of NO) by NTN glomeruli (95% inhibition). Proteinuria was exacerbated. There was no effect on early (24 hr) leukocyte infiltration. In the systemic form of the model arginine depletion by i.v. arginase increased glomerular thrombosis at 24 hours, and the severity of histological changes at four days, accompanied by systemic hypertension. In the unilateral form of the model, where i.v. arginase did not induce hypertension, there was no increase in thrombosis or histological severity of nephritis. These results show that arginine depletion, which inhibits glomerular NO synthesis in NTN, leads to increased proteinuria. Where injury is severe, or accompanied by systemic hypertension, the disease is further exacerbated by glomerular thrombosis. These results suggest that NO has an important role in limiting acute glomerular injury.
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PMID:L-arginine depletion inhibits glomerular nitric oxide synthesis and exacerbates rat nephrotoxic nephritis. 869 29

The present study was designed, first to investigate aortic arginase activity during the development and the establishment of mineralocorticoid-salt (DOCA-salt) hypertension, and second, to determine the relationship between arginase activity and blood pressure by giving a protein-supplemented diet (50% casein) known to increase hepatic arginase activity. Our results showed that aortic arginase activity in established hypertension of DOCA-salt rats was higher than in normotensive rats. The protein-supplemented diet (50% casein) accelerated the development of DOCA-salt hypertension. There was a positive correlation between arginase activity and the level of blood pressure in these DOCA-salt hypertensive rats fed 50% casein but not in DOCA-salt hypertensive rats on a normal (20% casein) diet. In normotensive rats, the protein-supplemented diet decreased aortic arginase activity and produced no change in systolic blood pressure. Our data suggest that aortic arginase activity is modified in established DOCA-salt hypertension and could participate in the physiopathology of arterial hypertension.
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PMID:Increased arginase activity in aorta of mineralocorticoid-salt hypertensive rats. 1068 26

In normotensive rats (NTR) and spontaneously hypertensive rats (SHR) with high (subgroup 1) and low (subgroup 2) level of the systemic arterial pressure (SAP) we studied an activity of arginase and nitric oxide synthase (NOS) in different tissues, and the content of their metabolites: urea and nitrit anion (NO2-). In isolated preparations of a thoracic aorta we recorded endothelium-dependent (ED) dilator reactions on acetylcholine (Ach). It has been found that in heart, aorta, plasma and erythrocytes of rats (subgroup 2) both the activity of arginase and content of urea increase remarkably. In heart, the activity of arginase reaches 27.96 +/- 5.92 nmol.min-1.mg-1 of protein, in aorta 4.74 +/- 0.99 nmol.min-1.mg-1 of protein (as compared with NTR 1.32 +/- 0.12 nmol.min-1.mg-1 of protein and 1.12 +/- 0.07 nmol.min-1.mg-1 of protein, accordingly). Content of urea in heart reaches 679.5 +/- 121.19 nmol.mg-1 of protein, in aorta 350.6 +/- 63.6 nmol.mg-1 of protein (in NTR it was 36.8 +/- 5.3 nmol.mg-1 of protein and 43.02 +/- +/- 9.55 nmol.min-1.mg-1 of protein, accordingly). It was followed with a decrease in the NOS activity and heterogeneous changes in NO2- content in the tissues under exploration. For example, the activity of NOS in heart and aorta decreased to 0.018 +/- 0.005 nmol.min-1.mg-1 of protein, in aorta 0.183 +/- 0.037 nmol.min-1.mg-1 of protein, accordingly, as compared to 0.093 +/- 0.014 nmol.min-1.mg-1 of protein and 0.41 +/- 0.07 nmol.min-1.mg-1 of protein in NTR. Content of NO2- in aorta decreased by 0.79 +/- 0.06 nmol.mg-1 of protein, but in heart it increased to 0.63 +/- +/- 0.13 nmol.mg-1 of protein, (in NTR it was 2.15 +/- 0.18 nmol.mg-1 of protein and 0264 +/- 0.04 nmol.min-1.mg-1 of protein, accordingly). In rats, subgroup 2, ED dilator responses of the smooth muscle (SM) of the thoracic aorta were inhibited by Ach (10(-6) mol). Their amplitude reduced by almost twice, and a latency for their response became 4 times as much. All the changes in the biochemical parametres in heart, aorta, plasma and erythrocytes, and changes in contractile activity of vascular SM proved to be also characteristic for rats in subgroup 1, but they were less expressed quantitatively. Thus, for the first time we have studied an activity of two alternative pathways for the metabolism of L-arginine on the model of arterial hypertension. The data obtained evidence that at hypertension non-oxidative (arginase) pathway of L-arginine metabolism is activated, while the oxidative pathway (NOS) is inhibited. Changes in the balance between them are followed with an essential inhibition of ED vasodilator responses. All this give us the prove to think of the origin for the arterial pressure increase to be both genetically and quantitatively determined damages in the biochemical homeostasis and dependent on it endothelial regulation of vascular tone.
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PMID:[Disorders of endothelium-dependent vascular reactions and of the arginase and NO-synthase pathways of L-arginine metabolism in arterial hypertension]. 1105 80

Have studied action of chronic urea--an arginase inhibitor--introduction (40 mg/kg, 28 days) on blood pressure, endothelium-dependent reactions of aorta smooth muscle cells (SMC) and nonenzymatic (contents of diene conjugates and H2O2) and enzymatic (contents of free arachidonic acid and vasoconstrictic eicosanoids LTC4 and TXA2) oxidizing lipid metabolism of heart, aorta, plasma and erythrocytes of spontaneously hypertensive rats. Have shown, that urea down regulate blood pressure without any normalization of endothelium-dependent reactions of SMC of aorta and down regulate both enzymatic and nonenzymatic oxidizing lipid metabolism. Down regulation of two alternative (by cyclooxygenase and by lipoxygenase) enzymatic pathways of free arachidonic acid oxidizing metabolism by urea can be one of mechanisms of its antihypertensive action. The possibility of urea use at hypertension and various pathophysiological conditions are discussed.
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PMID:[Inhibitors of arginase in the L-arginine metabolic pathway as a new class of antihypertensive drugs: effect of carbamide on lipid oxidative metabolism and on vessel tonus during arterial hypertension]. 1175 64

Effects of an antagonist of AT-1 receptors for angiotensin-II (Ang-II) irbezantane on the NO-synthase and arginase ways of the metabolism of L-arginine were studied in plasma and erythrocytes of the patients with arterial hypertension. The intensity of the non-oxidative arginase way of L-arginine metabolism in plasma and erythrocytes has been shown to be inhanced at hypertension versus the normotensive patients, while the activity of the alternative oxidative NO-synthase way was reduced. Inhibiting AT-1 receptors for Ang-II with high-affinity antagonist irbezantane normalized the ratio between two alternative ways of L-arginine metabolism through inhibiting the arginase way and reciprocal activating the NO-synthase way both in human plasma and erythrocytes.
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PMID:[Effect of irbesartan, an antagonist of AT-1 receptors for angiotensin II, on L-arginine metabolism in arterial hypertension]. 1212 80

Arginase catalyzes the hydrolysis of arginine to urea and ornithine. Urea is not only an important solute for concentrating urine but also inhibits Na-K-2Cl cotransport. To elucidate the roles of arginase in the development of salt-sensitive hypertension, we examined arginase activity and expression in the kidney and other organs of Dahl/Rapp salt-sensitive (SS) and salt-resistant (SR) rats before and after 4 weeks' administration of a 4% NaCl or control diet. At 4 weeks of age, arginase activity in the kidney was lower in SS rats than in SR rats. Kidney arginase activity was lower in SS rats than in SR rats at 8 weeks of age, and salt loading did not alter arginase activity. Arginase II (the dominant isoform in the kidney) mRNA and protein in the kidney of salt-loaded SS rats were also lower than those of salt-loaded SR rats. Arginase activities in the liver and cerebellum did not differ between SS and SR rats. To examine the effect of urea, the product of arginase reaction, on the development of hypertension, SS rats were given a 4% NaCl diet containing 5% kaolin or 5% urea. Six-week urea supplementation attenuated the development of hypertension in SS rats. These findings suggest that decreased arginase expression in the kidney may be at least partially responsible for the salt-sensitive hypertension in SS rats.
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PMID:Decreased expression of arginase II in the kidneys of Dahl salt-sensitive rats. 1213 20

This study was to examine whether the increase in aortic arginase activity observed in DOCA-salt hypertensive rats is involved in the mechanism of physiological hypertension by participating to vessel hypertrophy and/or to the impairment of endothelium-dependent relaxation to acethylcholine. We measured polyamine content and relaxation-response to acethylcholine in aortic rings isolated from control and DOCA-salt treated Sprague-Dawley rats after in vitro modification of arginase activity. Polyamine content was significantly increased in aorta from DOCA-salt hypertensive rats compared with controls. In the normotensive rats, the addition of L-valine (an inhibitor of arginase) decreased the relaxation response to acethylcholine whereas the addition of arginase increased the relaxation dependent response. On the contrary, in DOCA-salt hypertensive rats, the addition of L-valine or of arginase did not change the endothelium dependent relaxation. The results obtained suggest that the increase in aortic arginase activity in DOCA-salt hypertension could contribute to vascular hypertrophy but not to the impairment of endothelium-dependent relaxation.
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PMID:How could aortic arginase activity enhancement be involved in DOCA-salt hypertension? 1500 Feb 93

One characteristic of hypertension is a decreased endothelium-dependent nitric oxide (NO)-mediated vasodilation; however, the underlying mechanism is complex. In endothelial cells (ECs), L-arginine is the substrate for both NO synthase (NOS) and arginase. Because arginase has recently been shown to modulate NO-mediated dilation of coronary arterioles by reducing l-arginine availability, we hypothesized that upregulation of vascular arginase in hypertension contributes to decreased NO-mediated vasodilation. To test this hypothesis, hypertension (mean arterial blood pressure >150 mm Hg) was maintained for 8 weeks in pigs by aortic coarctation. Coronary arterioles from normotensive (NT) and hypertensive (HT) pigs were isolated and pressurized for in vitro study. NT vessels dilated dose-dependently to adenosine (partially mediated by endothelial release of NO) and sodium nitroprusside (endothelium-independent vasodilator). Conversely, HT vessels exhibited reduced dilation to adenosine but dilated normally to sodium nitroprusside. Adenosine-stimulated NO release was increased approximately 3-fold in NT vessels but was reduced in HT vessels. Moreover, arginase activity was 2-fold higher in HT vessels. Inhibition of arginase activity by N(omega)-hydroxy-nor-l-arginine or incubation with l-arginine partially restored NO release and dilation to adenosine in HT vessels. Immunohistochemistry showed that arginase expression was increased but NOS expression was decreased in arteriolar ECs of HT vessels. These results suggest that NO-mediated dilation of coronary arterioles is inhibited in hypertension by an increase in arginase activity in EC, which limits l-arginine availability to NOS for NO production. The inability of arginase blockade or l-arginine supplementation to completely restore vasodilation may be related to downregulation of endothelial NOS expression.
Hypertension 2004 Dec
PMID:Upregulation of vascular arginase in hypertension decreases nitric oxide-mediated dilation of coronary arterioles. 1549 30

Vascular tissues express arginase that metabolizes L-arginine to L-ornithine and urea and thus reduces substrate availability for nitric oxide formation. Dahl salt-sensitive (Dahl-S) rats with salt-induced hypertension show endothelial dysfunction, including decreased vascular nitric oxide formation. This study tests the hypothesis that increased vascular arginase activity contributes to endothelial dysfunction in hypertensive Dahl-S rats. Male Dahl-S rats (5-6 wk) were placed on high (8%) or low (0.3%) NaCl diets for 4 wk. With respect to the low-salt group, mean arterial blood pressure was increased in the high-salt animals. Immunohistochemical stainings for arginase I and II were enhanced in arterioles isolated from high-salt Dahl-S rats. Experiments used isolated Krebs buffer-superfused first-order gracilis muscle arterioles with constant pressure (80 mmHg) and no luminal flow or constant midpoint but altered endpoint pressures to establish graded levels of luminal flow (0-50 microl/min). In high-salt arterioles, responses to an endothelium-dependent vasodilator acetylcholine (1 nmol/l to 3 micromol/l) and flow-induced dilation were decreased. Acute in vitro treatment with an inhibitor of arginase, 100 micromol/l (S)-(2-boronoethyl)-L-cystine, or the nitric oxide precursor, 1 mmol/l L-arginine, similarly enhanced acetylcholine and flow-induced maximal dilations and abolished the differences between high- and low-salt arterioles. These data show that arteriolar arginase expression is increased and that endothelium-dependent vasodilation is decreased in high-salt Dahl-S rats. Acute pretreatment with an arginase inhibitor or with L-arginine restores endothelium-dependent vasodilation and abolishes the differences between high- and low-salt groups. These results suggest that enhanced vascular arginase activity contributes to endothelial dysfunction in Dahl-S rats with salt-induced hypertension and identifies arginase as a potential therapeutic target to prevent endothelial dysfunction.
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PMID:Arginase inhibition restores arteriolar endothelial function in Dahl rats with salt-induced hypertension. 1559 Nov 55

Arginine, a semi-essential amino acid, plays a major nutritional and metabolic role. In particular, arginine is the precursor of nitric oxide which is involved in the endothelial function. Several factors, such as hypercholesterolemia, diabetes, ageing and hypertension are established risk factors for atherosclerosis, in particular by decreasing the availability of nitric oxide. Thus, endothelial nitric oxide synthase has a pivotal role against atherosclerosis. A suitable amount of cofactor and a sufficient intake of arginine have been shown to modulate nitric oxide-induced vasodilatation: despite the fact that the intracellular concentration of arginine is well above the Km of endothelial nitric oxide synthase, an arginine supplemented-diet is effective in increasing the production of nitric oxide. Several mechanisms have been proposed to explain this "arginine paradox": co-localization of the arginine transporter with endothelial nitric oxide synthase, intracellular arginine regeneration from citrulline, balance between endothelial arginase and nitric oxide synthase. Statins which are HMG-CoA reductase inhibitors inhibit the synthesis of mevalonate, and thus that of cholesterol. In addition, statins increase the stabilization of endothelial nitric oxide synthase mRNA. The co-operation between cholesterol synthesis and the upregulation of caveolin-1 on the one hand, and the activation of endothelial nitric oxide synthase on the other hand, is very tight. A depletion of cholesterol in the caveolae induces a decrease in caveolin-1 at the cell surface allowing NOS activation. Thus statins improve nitric oxide production and vasodilatation. In a recent work in the hypercholesterolemic Watanabe rabbit, we have demonstrated that the combination of arginine with a statin, namely atorvastatin, significantly hinders the spreading of atherosclerotic plaques as compared with monotherapies. Such association of a nutriment and a drug open a new area of therapeutic strategy.
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PMID:[Arginine and statins: relationship between the nitric oxide pathway and the atherosclerosis development]. 1623 Feb 78


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