UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The contribution of the local vascular production of angiotensin-(1-7) [Ang-(1-7)] to the control of alpha-adrenergic-induced contractions in the aorta of Sprague-Dawley (SD) and TGR(mRen-2)27 [mRen-2] rats was studied. 2. In mRen-2 rats, contractile responses to phenylephrine were diminished as compared to control SD rats in endothelium containing but not in endothelium-denuded vessels. L-NAME increased contractile responses to phenylephrine in mRen-2 rats and, after nitric oxide synthase blockade, responses to phenylephrine became comparable in both strains. 3. Inhibition of angiotensin-converting enzyme (ACE) by captopril potentiated contractile responses in mRen-2 rats and diminished contractile responses in SD rats, both effects being dependent on the presence of a functional endothelium. The effect of captopril in mRen-2 rats was abolished in vessels pre-incubated with Ang-(1-7). 4. Blockade of Ang-(1-7) and bradykinin (BK) receptors by A-779 and HOE 140 respectively, increased phenylephrine-induced contraction in mRen-2, but not in SD rats. This effect was seen only in endothelium-containing vessels. 5. Angiotensin II AT(1) and AT(2) receptor blockade by CV 11974 and PD 123319 did not affect the contractile responses to phenylephrine in aortas of transgenic animals but diminished the response in SD rats. This effect was only seen in the presence of a functional endothelium. 6. It is concluded that the decreased contractile responses to phenylephrine in aortas of mRen-2 rats was dependent on an intact endothelium, the local release and action of Ang-(1-7) and bradykinin.
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PMID:Angiotensin-(1-7) is involved in the endothelium-dependent modulation of phenylephrine-induced contraction in the aorta of mRen-2 transgenic rats. 1193 15

The purpose of the present study was to investigate the effect of angiotensin II (Ang II) on nitric oxide (NO) concentration and its signal transduction pathway in cultured neonatal rat cardioymocytes. NO content was measured in cultured neonatal rat cardiomyoctes using a nitrite/nitrate colormetric method kit. NO content was represented by measured nitrite (NO(2)) and nitrate (NO(3)) level (NO(2)/NO(3)). The results are as follows. NO production was decreased by Ang II in a dose dependent manner but increased by L Arg. The Saralasin, an antagonist of Ang II receptor, inhibited the effect of Ang II on NO production. The effect of Ang II on NO production was inhibited by NOS blocker N(G)-nitro-L-arginine methyl ester L-NAME but not by L-Arg. Pretreatment of Phorbol 12-myristate 13-acetate PMA , a PKC activator, decreased NO concentration significantly. This effect was strengthened by L-NAME. Staurosporine, a PKC inhibitor, abolished the inhibiting effect of Ang II on production of NO. The above results suggest that Ang II could decrease NO content in cultured neonatal rat cardiomyocytes significantly. Activity of NOS may be inhibited by Ang II. Ang II receptor was involved in the inhibitory effect of Ang II on NO production. Activation of protein kinase C (PKC) decreased significantly NO production in cultured neonatal rat cardiomyoctes, which appears to be associated with PKC in the signal transduction pathway.
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PMID:[Effect of protein kinase C on inhibition of nitric oxide synthesis in cultured neonatal rat cardiomyocytes by angiotensin II]. 1195 Nov 15

We investigated a possible contribution of nitric oxide (NO) and prostaglandins to the inhibitory effect of losartan on contractions to Ang I (10(-6) M) and Ang II (10(-7) M) with or without L-NAME (10(-4) M) or indomethacin (10(-5) M) in the aorta of WKY, SHR and hamster (n=7 each). Rings of thoracic aorta (2-mm long) were placed in a myograph (5 ml). Endothelium-dependent vasodilations were evaluated with acetylcholine (10(-8) to 10(-6) M). After a 45-minute incubation with L-NAME under a resting tension of 2 g, only hamster aorta contracted (p<0.01). The SHR aorta showed impaired relaxations to acetylcholine compared with the WKY and hamster aorta (p<0.05). Despite the difference in the stimulated NO release, losartan completely abolished the responses to Ang I and Ang II both in WKY and SHR vessels irrespective of the presence of L-NAME. In contrast to the rat aorta, the inhibitory effect of losartan was attenuated in the presence of L-NAME in the hamster aorta (78% vs 99% inhibition, p<0.05). Indomethacin did not alter the effect of losartan in any vessels. Our results suggest that the presence of NO, particularly a basal secretion of NO, is necessary for the full expression of the inhibitory effect of losartan in the hamster, but not in WKY or SHR, aorta. Unlike NO, prostaglandins do not appear to play a role in the effect of losartan.
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PMID:Nitric oxide mediates inhibitory effect of losartan on angiotensin-induced contractions in hamster but not rat aorta. 1196 11

Two distinct subtypes of angiotensin (Ang) II receptors, type 1 (AT(1)) and type 2 (AT(2)), have been identified. Vascular smooth muscle cells (VSMCs) usually express AT(1) receptor. To elucidate the direct effects of the AT(2) receptor on the AT(1) receptor in VSMCs, we transfected AT(2) receptor gene into cultured rat VSMCs. Overexpression of AT(2) receptor significantly decreased expression of AT(1a) receptor at both the mRNA and protein levels in the presence and absence of Ang II in VSMCs. Overexpression of AT(2) receptor increased expression of bradykinin and inducible NO in the presence and absence of Ang II in VSMCs. Bradykinin B(2) receptor antagonist HOE-140 and NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) inhibited the decreases in AT(1a) receptor expression by the overexpression of AT(2) receptor in VSMCs. L-Arginine augmented the decrease in AT(1a) receptor expression. Overexpression of AT(2) receptor suppressed basal DNA synthesis and proliferation of VSMCs and abolished response of DNA synthesis to Ang II in VSMCs. Our results demonstrate that overexpression of the AT(2) receptor downregulates AT(1a) receptor expression in rat VSMCs in a ligand-independent manner that is mediated by the bradykinin/NO pathway. Downregulation of AT(1a) receptor is a novel mechanism by which the AT(2) receptor regulates growth and metabolism of VSMCs.
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PMID:Angiotensin II type 2 receptor gene transfer downregulates angiotensin II type 1a receptor in vascular smooth muscle cells. 1201 86

Although accumulating lines of evidence indicate the proangiogenic role of angiotensin II (Ang II), little is known about the molecular mechanisms associated with such an effect. This study aimed to identify molecular events involved in Ang II-induced angiogenesis in the Matrigel model in mice. C57Bl/6 female mice received a subcutaneous injection of either Matrigel or Matrigel with Ang II (10(-7) M) alone, with Ang II and an AT1 receptor antagonist (candesartan, 10(-6) M), or with Ang II and AT2 receptor antagonist (PD123319, 10(-6) M). After 14 days, angiogenesis was assessed in the Matrigel-plug by histological evaluation and cellular counting. Ang II increased by 1.9-fold the number of cells within the Matrigel (p < 0.01 versus control). Immunohistological analysis revealed the presence of macrophages, endothelial and smooth muscle cells, and the development of vascular-like structure. Such an angiogenic effect was associated with an increase in vascular endothelial growth factor (VEGF) (1.5-fold, p < 0.01), endothelial nitric oxide (eNOS) (1.7-fold, p < 0.01), and cyclooxygenase-2 (1.4-fold, p < 0.05) protein levels measured by Western blotting. Conversely, Ang II treatment did not affect MMP-9 and MMP-2 activity, assessed by zymography. Blockade of AT1 receptor completely prevented the Ang II-induced angiogenesis and protein regulations, whereas that of AT2 was ineffective. Administration of VEGF neutralizing antibody (2.5 microg ip twice a week) and cyclooxygenase-2 selective inhibitor (nimesulide, 30 mg/L) also hampered Ang II proangiogenic effect. In addition, Ang II-induced cell ingrowth was impaired by treatment with nitric oxide synthase inhibitor (L-NAME, 10 mg/kg/day) and in eNOS-deficient mice. Therefore, in an in vivo model, Ang II induced angiogenesis through AT1 receptor, which involved activation of VEGF/eNOS-related pathway and of the inflammatory process.
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PMID:Angiotensin II angiogenic effect in vivo involves vascular endothelial growth factor- and inflammation-related pathways. 1206 85

Different changes in glomerular filtration rates (GFR) in deep and superficial glomeruli have been suggested to influence renal NaCl excretion and concentrating ability. Angiotensin II (AngII) has been implicated in such changes, but the experimental evidence has been conflicting, probably because of the methodological limitation of just one 'snapshot' measurement of local GFR per kidney. We have therefore studied the effect of AngII and AT(1)-receptor blockade on glomerular filtration in outer, middle and inner cortex (OC, MC and IC, respectively) in pentobarbitone-anaesthetised rats using the aprotinin (Ap) method, providing control and experimental measurements in the same kidney. Glomerular filtration rate per gram cortical tissue was measured based on 'free' glomerular filtration of Ap followed by complete tubular uptake and a 20 min sojourn in the proximal tubular cells before breakdown and incipient return to the plasma.(125)I-labelled Ap was injected I.V. to determine control Ap clearance, followed after 13 min by injection of AngII or the A1 type AngII receptor blocker losartan and 2 min thereafter by (131)I-labelled Ap to determine clearance in the experimental period. Tracer activity in frequent blood samples and in tissue samples allowed calculation of GFR in the two periods. Mean GFR control values were: 1.13 ml min(-1) in whole kidney and 1.44, 1.27 and 0.76 ml min(-1) per gram cortical tissue in OC, MC and IC, respectively. The most sensitive and comprehensive measure of altered GFR distribution is the ratio between the relative filtration change in inner versus that in outer cortex, F = (IC(E)/IC(C))/(OC(E)/OC(C)), where subscripts E and C stand for experimental and control, respectively. F values greater than 1.00 directly indicate and quantify a relatively greater increase of filtration rate in inner than in outer cortex. We found in salt-replete rats that at practically unchanged total GFR, intravenous and intra-arterial infusion of AngII increased F to 1.07 and 1.04 (P < 0.05) whereas losartan reduced F to 0.99. After pretreatment with the inhibitor of nitric oxide production L-NAME, losartan increased total GFR by 8 % and F fell to 0.95 (P < 0.05). In salt-depleted rats losartan reduced F to 0.95 (P < 0.05) at unchanged total GFR. All IC/OC changes induced by losartan were significantly different from that obtained by AngII infusions. We conclude that deep nephrons have higher postglomerular AngII tone and also higher AngII sensitivity than superficial nephrons. The better preserved GFR in deep cortex during AngII action may contribute towards maintaining the renal concentrating ability by providing NaCl for reabsorption by the ascending limb of the loop of Henle.
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PMID:Effect of exogenous and endogenous angiotensin II on intrarenal distribution of glomerular filtration rate in rats. 1206 62

The aim of this study was to determine the molecular mechanism of nitric oxide (NO) in preventing cardiomyocytes from hypertrophic response induced by angiotensin II (Ang II). Hypertrophic response of neonatal rat cardiomyocytes was assayed by protein synthesis rate and expression of atrial natriuretic peptide (ANP) mRNA. The level of NO was shown by the content of nitrate and nitrite in cardiac myocytes. The protein expression of MKP-1 and the gene expression of eNOS were measured with Western blotting and RT-PCR, respectively. The results are as follows. (1) L-arginine (L-Arg) induced a dose-dependent increase in NO by 16% and 31% at the concentrations of 10 micromol/L and 100 micromol/L, respectively. L-Arg also increased the gene expression of eNOS. However, these effects were inhibited by L-NAME, the inhibitor of NOS. (2) The gene expression and the protein synthesis of ANP induced by Ang II (0.1 micromol/L) were inhibited by L-Arg (100 micromol/L). The inhibitory action of L-Arg was abolished after pretreatment with antisense oligoneucleotide against MKP-1. (3) L-Arg (100 micromol/L) increased the protein expression of MKP-1 by 225%, which was inhibited by L-NAME, an NOS inhibitor, and KT-5823, a cGMP-dependent protein kinase (PKG) inhibitor. However, Ang II enhanced the effect induced by L-Arg. The above results show that NO may activate PKG, and thereby promote the protein expression of MKP-1 and inactivate MAPK, resulting in an inhibition of cardiomyocyte hypertrophic response induced by Ang II.
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PMID:[Molecular mechanism of nitric oxide in preventing cardiomyocytes from hypertrophic response induced by angiotensin II]. 1207 67

Hypertension is closely associated with vascular endothelial dysfunction. The aim of this study was to investigate the effects of Angiotensin II (ANG II) receptor antagonist losartan on the blood-brain barrier (BBB) permeability in L-NAME-induced hypertension and/or in ANG II-induced acute hypertension in normotensive and hypertensive rats. Systolic blood pressure was measured by tail cuff method before, during and following L-NAME treatment (1 g/L). Losartan (3 mg/kg) was given to the animal for five days. Acute hypertension was induced by ANG II (60 microg/kg). Arterial blood pressure was directly measured on the day of the experiment. BBB disruption was quantified according to the extravasation of the albumin-bound Evans blue dye. Losartan significantly reduced the mean arterial blood pressure from 169 +/- 3.9 mmHg to 82 +/- 2.9 mmHg in L-NAME and from 171 +/- 2.9 mmHg to 84 +/- 2.9 in L-NAME plus losartan plus ANG II groups (p < 0.05). The content of Evans blue dye in the cerebral cortex significantly increased in L-NAME (p < 0.01). Moreover, the content of Evans blue dye markedly increased in the cerebellum (p < 0.001) and slightly increased in diencephalon region (p < 0.05) in L-NAME plus ANG II. Losartan reduced the increased BBB permeability to Evans blue dye in L-NAME (p < 0.01) and L-NAME plus ANG II (p < 0.001). These results indicate that L-NAME and L-NAME plus ANG II both lead to an increase in microvascular Evans blue dye efflux to brain, and losartan treatment attenuates this protein-bound dye transport into brain tissue presumably due to its protective effect on endothelial cells of brain vessels.
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PMID:Effects of losartan on the blood-brain barrier permeability in long-term nitric oxide blockade-induced hypertensive rats. 1208 90

The hypotensive effect of RuNO was investigated in acute and chronic hypertensive rats, as well as in normotensive rats. Acute hypertension rats were used with 30% increase on basal BP (phenylephrine, angiotensin II (Ang II), N(G)-nitro-L-arginine methyl ester (L-NAME), and adult spontaneously hypertensive rats (SHR) (basal BP 168 +/- 3 mm Hg) were used as models for chronic hypertension. Rats were implanted with catheters (iv/ia) for BP measurements and for in bolus administration of RuNO, sodium nitroprusside (SNP), and acetylcholine (Ach) (10, 20, 40 nmol/kg, iv). The principal findings of this study were: (i) The hypotensive response to RuNO was 150% higher in acutely (phenylephrine and Ang II) and chronically (SHR) hypertensive rats than in normotensive rats, except in the case of L-NAME-induced hypertension (deltaMAP = 10 +/- 1.4 mm Hg). Chronic SHR showed 60% increase (deltaMAP = 19 +/- 0.8 mm Hg) in the effect compared to normotensive rats. (ii) The hypotensive response to SNP was lower (60%) in hypertensive rats than in normotensive rats, when compared to RuNO. However, the responses were similar in L-NAME-induced hypertension (deltaMAP = 30 +/- 2 mm Hg). (iii) The vasodilator response to Ach was increased in rats with Ang II-induced hypertension (deltaMAP = 53 +/- 1 mm Hg) and in SHR (deltaMAP = 67 +/- 3 mm Hg). RuNO response was more potent than SNP in hypertensive models and the increment in relation to normotensive was observed in the phenylephrine- and L-NAME-treated rats. This response could be correlated to the different endothelial dysfunction present in each model.
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PMID:A new inorganic vasodilator, trans-[Ru(NO)(NH(3))(4)(POEt)(3)](PF(6))(3): hypotensive effect of endothelium-dependent and -independent vasodilators in different hypertensive animals models. 1217 20

Long-term inhibition of nitric oxide synthase (NOS) in rats is known to cause systemic hypertension and renal parenchymal injury. We have previously reported that activation of intra-renal renin-angiotensin system was a major contributing factor for renal injury in chronically NOS-inhibited rats. Massive interstitial infiltration of monocytes/macrophages (M/M) was characteristically seen in this model. The present study was performed to elucidate the role of chemokines, RANTES and MCP-1, in promoting M/M recruitment into the renal cortex. The number of infiltrating ED-1-positive cells was examined in association with the level of expression of RANTES and MCP1 mRNAs in the renal cortex of rats treated orally for 12 weeks with L-NAME. Compared to controls rats, the number of infiltrating ED-1-positive cells was significantly higher in L-NAME-treated rats. The mRNA expressions of both RANTES and MCP-1 were significantly higher in L-NAME-treated rats than the control. In L-NAME-treated rats, the high number of ED-1-positive cells and increased expression of both RANTES and MCP-1 were suppressed by ACE inhibitor, but not by hydralazine. In contrast, neither ED-1 counts nor RANTES mRNA expression were affected by angiotensin (Ang) II type 1 receptor antagonist. These results suggest the likely involvement of RANTES and MCP-1 in the recruitment of M/M into the renal cortex of rats with chronic NOS inhibition. Furthermore, it is also indicated that Ang II stimulates MCP-1 expression via Ang II type 1 receptor, whereas RANTES expression is mediated via Ang II type 2 receptor.
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PMID:MCP-1 and RANTES are expressed in renal cortex of rats chronically treated with nitric oxide synthase inhibitor. Involvement in macrophage and monocyte recruitment. 1218 99

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