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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the angiotensin-II (AII) agonists and antagonists on both 125I-SARILE binding and phosphoinositol (PI) accumulation in clone 9 cells were examined. Clone 9 cells, which are derived from rat liver, have been shown to respond to AII agonists with an increase in PI accumulation which is inhibitable by Sar1,Ile8-AII (SARILE) and DUP-753 but not PD-123319, suggesting that they possess the AT1 subtype of AII receptor. The present results confirmed these properties. The order of potency of AII agonists was AII > AIII > AI. Clone 9 cells also possessed binding sites for 125I-SARILE. The majority of these were AT1 type receptors, although a small number of AT2 receptors may also have been present. The order of potency of AII agonists in inhibiting 125I-SARILE binding was AII >> AIII = AI. The difference in rank order of potency between the functional and binding assay was due to AIII being much less potent in the binding assay than the functional assay. Since the potency of AIII relative to AII was lower than that at either AT1 or AT2 subtypes of AII receptor, these data suggest that an additional subtype, with selectively low affinity for AIII, exists.
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PMID:Comparison of the binding and functional actions of angiotensin agonists in clone 9 cells: additional evidence for angiotensin II receptor heterogeneity. 839 80

We investigated the effect of losartan (DUP-753) on the dipsogenic responses produced by intracerebroventricular (icv) injection of noradrenaline (40 nmol/microliters) and angiotensin II (ANG II) (2 ng/microliters) in male Holtzman rats weighing 250-300 g. The effect of DUP-753 was also studied in animals submitted to water deprivation for 30 h. After control injections of isotonic saline (0.15 M NaCl, 1 microliter) into the lateral ventricle (LV) the water intake was 0.2 +/- 0.01 ml/h. DUP-753 (50 nmol/microliters) when injected alone into the LV of satiated animals had no significant effect on drinking (0.4 +/- 0.02 ml/h) (N = 8). DUP-753 (50 nmol/microliters) injected into the LV prior to noradrenaline reduced the water intake from 2.4 +/- 0.8 to 0.8 +/- 0.2 ml/h (N = 8). The water intake induced by injection of ANG II and water deprivation was also reduced from 9.2 +/- 1.4 and 12.7 +/- 1.4 ml/h to 0.8 +/- 0.2 and 1.7 +/- 0.3 ml/h (N = 6 and N = 8), respectively. These data indicate a correlation between noradrenergic pathways and angiotensinergic receptors and lead us to conclude that noradrenaline-induced water intake may be due to the release of ANG II by the brain. The finding that water intake was reduced by DUP-753 in water-deprived animals suggests that dehydration releases ANG II, and that AT1 receptors of the brain play an important role in the regulation of water intake induced by deprivation.
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PMID:Inhibitory effect of DUP-753 on the drinking responses of rats to central administration of noradrenaline and angiotensin II and to dehydration. 873 16

We determined the effect of intracerebroventricular (icv) administration of losartan, an angiotensin II (ANG II) subtype 1 receptor (AT1) antagonist, on icv carbachol-induced natriuresis, kaliuresis and antidiuresis in water-loaded male Holtzman rats (250-300 g) with a cannula implanted into the lateral ventricle (LV). The rats were water loaded with 5% of their body weight by gavage twice, with the second gavage one hour after the first. Carbachol (2 nmol in 1 microliter) was injected icv immediately after the second load. When losartan (DUP-753, 50 nmol in 1 microliter) was administered icv, it was given 3 min before carbachol. Previous icv treatment with losartan significantly reduced the icv carbachol-induced natriuresis (324 +/- 17 microEq/120 min), kaliuresis (103 +/- 15 microEq/120 min) and antidiuresis (13.5 +/- 2.1 ml/120 min) compared to the effects of previous icv injection of saline (Na+ excretion = 498 +/- 22 microEq/120 min; K+ excretion = 167 +/- 20 microEq/120 min; urine volume = 5.2 +/- 1.2 ml/120 min). These results, reported as means +/- SEM for 12 rats in each group, are consistent with the hypothesis that AT1 subtype receptors participate in the regulation of body electrolyte balance.
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PMID:Losartan (DUP-753) blocks the natriuretic, kaliuretic and antidiuretic effect of intracerebroventricular injection of carbachol in water-loaded rats. 873 17

We have previously demonstrated that two isoforms (AT1A and AT1B) of the angiotensin II (ANG II) type 1 (AT1) receptor exist in the rat kidney and are differentially regulated by a low-sodium diet. The present experiment was designed to test the hypothesis that sodium deficiency upregulates AT1A and AT1B gene expression in the adrenal gland by activating the AT1 receptor. Wistar rats (7 wk old) were divided into four groups (n = 10 each) and fed normal sodium (0.5%; NS), NS plus 3 mg.kg-1.day-1 losartan (DUP-753; i.e., DUP), low sodium (0.07%; LS), and LS plus DUP. After 2 wks, body weight and mean arterial pressure were not different (P > 0.05). Northern blot analysis showed that the ratio of AT1A: glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA in the adrenal gland was increased (P < 0.001) by 172% in LS but was unchanged in NS + DUP and LS + DUP vs. NS. The ratio of adrenal AT1B:GAPDH mRNA was increased (P < 0.001) by 245% in LS and unchanged in NS + DUP and LS + DUP vs. NS. Radioligand binding indicated that AT1 receptors (fmol/mg protein) in the adrenal gland were increased in LS (141 +/- 17; P < 0.001) vs. NS (54 +/- 3), NS + DUP (43 +/- 5), and LS + DUP (56 +/- 6). We conclude that sodium deficiency increases both AT1A and AT1B gene expression and elevates the AT1 receptor density in the adrenal gland. Blockade of the binding of ANG II to the AT1 receptor by losartan prevents the increases in AT1A and AT1B mRNA expression and the AT1 receptor density induced by sodium depletion, suggesting that these changes in the adrenal gland are mediated by activation of the AT1 receptor. These results will provide a basis for future experiments to further elucidate transcriptional regulation or functional activity of each of the receptor subtypes.
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PMID:Regulation of ANG II-receptor subtype and its gene expression in adrenal gland. 877 82

In the present study, 3-day treatment of nondifferentiated NG108-15 cells with 100 nM angiotensin II (Ang II) induces morphological differentiation of neuronal cells characterized by the outgrowth of neurites. These morphological changes are correlated with an increase in the level of polymerized tubulin and in the level of the microtubule-associated protein, MAP2c. Mediation by the AT2 receptor may be inferred since: (a) these cells contain only AT2 receptors; (b) the effects are mimicked by CGP 42112 (an AT2 receptor agonist); (c) they are not suppressed by the addition of DUP 753 (an AT1 receptor antagonist); and (d) are abolished by co-incubation with PD 123319 (an AT2 receptor antagonist). Application of Ang II in dibutyryl cAMP-differentiated cells (which contain both types of receptors) induces neurite retraction, an effect mediated by the AT1 receptor. These results indicate that the AT2 receptor of Ang II induces neuronal differentiation, which is initiated through an increase in the levels of MAP2c associated with tubulin. Moreover, our results demonstrate that the AT1 receptor inhibit the process of differentiation induced by dibutyryl cAMP, whereas the AT2 receptors potentiate this effect, illustrating negative cross-talk interaction between the two types of Ang II receptors.
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PMID:Angiotensin II induction of neurite outgrowth by AT2 receptors in NG108-15 cells. Effect counteracted by the AT1 receptors. 879 47

The aim of the present study was to characterize distribution and pharmacological properties of angiotensin II (Ang II) receptors in human fetal adrenals frozen immediately after removal. Autoradiographic studies indicate that Ang II receptors are present throughout the gland. Coincubations with DUP 753, a specific antagonist of the AT1 receptor, and with PD 123319, a specific antagonist of the AT2 receptor, reveal that Ang II receptors are mainly of the type 2. The AT1 receptors are detected after 16 weeks of gestation at the periphery of the gland. Binding of 125I-Ang II to membrane preparations is dose-dependent and saturable. Competition studies and Scatchard analysis reveal a homogenous population of high-affinity AT2 binding sites (Kd = 0.68 +/- 0.1 nmol/L). Binding capacities decrease from 1080 +/- 304 fmol/mg protein at 14 weeks to 275 +/- 55 fmol/mg protein at 21 weeks. However, when fetal adrenal cells are prepared and cultured for 6 days, the proportion of AT1 receptors increases, indicating that culture conditions induce expression of the AT1 receptor. These results differ from those obtained in adult glands, where autoradiographic studies reveal that the AT1 receptors are found mainly in zona glomerulosa and AT2 receptors mainly in the medulla. These data suggest that the AT2 receptors could be involved in the morphological or functional differentiation of the human fetal adrenal gland.
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PMID:The angiotensin AT2 receptor is present in the human fetal adrenal gland throughout the second trimester of gestation. 892 38

In the present study, we have characterized distribution and pharmacological properties of angiotensin II (Ang II) receptors in human adrenals frozen immediately after removal. Autoradiographic studies indicate that Ang II receptors are present throughout the gland. Co-incubations with DUP 753, a specific antagonist of the AT1 receptor, and with PD 123319, a specific antagonist of the AT2 receptor, reveal that Ang II receptors are mainly of type 2. The AT1 receptors are detected after 16 weeks of gestation at the periphery of the gland. Competition studies and Scatchard analysis reveal a homogenous population of high affinity AT2 binding sites (Kd = 0.68 +/- 0.1 nM). Binding capacities decrease from 1080 +/- 304 fmol/mg protein at 14 weeks to 275 +/- 55 fmol/mg protein at 21 weeks. These results differ from those obtained in adult glands where autoradiographic studies reveal that the AT1 receptors are found mainly in the zona glomerulosa and AT2 receptors mainly in the medulla. These data suggest that the AT2 receptors could be involved in the morphological or functional differentiation of the human fetal adrenal gland.
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PMID:Angiotensin II receptors in the human adrenal gland. 896 83

We investigated the tolerability and angiotensin II antagonist activity of oral DuP 532 in healthy male subjects. DuP 532 (1 to 200 mg) was well tolerated, with no effect on blood pressure or heart rate. Compared with losartan (100 mg), DuP 532 (200 mg) was a weak antagonist of pressor responses to intravenous angiotensin II. Maximum inhibition of diastolic pressor response was 86% (95% confidence interval [CI], 84%, 88%) approximately 4.6 hours after losartan and 48% (95% CI, 38%, 56%) 8.7 hours after DuP 532. Twenty-four hours after dosing, inhibition by losartan and DuP 532 was similar (40% to 45%). DUP 532 is extensively bound in human plasma, with an in vitro free fraction of 0.06. Although DuP 532 and EXP3174 (losartan's active metabolite) have similar AT1-receptor potency, and plasma concentrations of DuP 532 were much greater than losartan/EXP3174, the level of antagonism was much less for DuP 532. These results indicate that multiple factors determine the in vivo potency of angiotensin II antagonists, including affinity for and distribution to the receptor as modulated by plasma binding.
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PMID:DuP 532, an angiotensin II receptor antagonist: first administration and comparison with losartan. 902 74

Clinical data suggest a link between the activation of the renin-angiotensin system and cardiovascular ischemic events. Leukocyte accumulation in the vessel wall is a hallmark of early atherosclerosis and plaque progression. E-Selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) are adhesion molecules participating in mediating interactions between leukocytes and endothelial cells and have been found to be expressed in athero-sclerotic plaques. We investigated whether angiotensin II, the effector of the renin-angiotensin system, influences the endothelial expression of E-selectin, VCAM-1, and ICAM-1. In coronary endothelial cells derived from explanted human hearts, angiotensin II (10(-11) to 10(-5) mol/L) induced a concentration-dependent increase in E-selectin expression. The effect was measured by cell ELISA and duplex reverse-transcription polymerase chain reaction (RT-PCR) and reached its maximum at 10(-7) mol/L. Angiotensin II induced only a small increase in E-selectin expression in cardiac microvascular endothelial cells. VCAM-1 and ICAM-1 were not affected by angiotensin II stimulation. In addition, the effect of angiotensin II-induced E-selectin expression on leukocyte adhesion was quantified under flow conditions. Angiotensin II (10(-7) mol/L) increased leukocyte adhesion significantly to 67% of the maximal effect by tumor necrosis factor-alpha at a wall shear stress of 2 dyne/cm2. This adhesion was found to be E-selectin dependent, as demonstrated by blocking antibodies. The AT1-receptor antagonist DUP 753 significantly reduced E-selectin-dependent adhesion, whereas the AT2-receptor antagonist PD 123177 had no inhibitory effect. In addition, only AT1-receptor, but not AT2-receptor, mRNA could be detected by RT-PCR in coronary endothelial cells. Therefore, it is suggested that AT1 receptors mediate the effects of angiotensin II on E-selectin expression and leukocyte adhesion on coronary endothelial cells.
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PMID:Angiotensin II-induced leukocyte adhesion on human coronary endothelial cells is mediated by E-selectin. 935 54

We have previously shown that angiotensin II(3-7) [Ang II(3-7)] stimulates behavioural activity of rats similar to angiotensin II (Ang II). The involvement of AT1 angiotensin receptors in stimulating the behavioural activity of rats, using their selective ligand losartan (DUP 753), was examined. Ang II(3-7), given intracerebroventricularly (i.c.v.) at a dose of 1 nmol, significantly enhanced recall of a passive avoidance behaviour, object recognition, learning of conditioned avoidance responses (CARs) and apomorphine (1 mg kg-1, i.p.) stereotypy. Losartan (1 microgram, i.c.v.) did not alter any of the behaviours except for that measuring anxiety which was diminished both, in peptide treated and in control rats. On the other hand, losartan abolished Ang II(3-7) facilitation of recall of the passive avoidance, object recognition and the increase in apomorphine stereotypy. Losartan did not influence the increased rate of CARs acquisition after the peptide. None of the treatments significantly changed locomotor activity estimated in an open field. These data point to some involvement of AT1 angiotensin receptors in the behavioural activity of Ang II(3-7).
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PMID:Losartan influences behavioural effects of angiotensin II(3-7) in rats. 942 16


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