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

The expression of angiotensin AT1A and AT1B receptor mRNA after continuous angiotensin II administration was investigated in the rat adrenal gland. Angiotensin AT1 receptor mRNA detected by Northern blot analysis decreased to 52.7+/-16.1% of control after the administration of angiotensin II (20 microg/h) for 24 h, and to 70.8+/-8.0% after 1 week. A low dose of angiotensin II (0.2 microg/h) also decreased angiotensin AT1 receptor mRNA to 73.0+/-5.5% after 1 week. Competitive reverse transcription and polymerase chain reaction (RT-PCR) experiments revealed that both angiotensin AT1A and AT1B receptor mRNAs decreased after administration of angiotensin II (20 or 0.2 microg/h) for 1 week. Analysis of the angiotensin AT1A promoter by using luciferase-reporter system showed that angiotensin II (up to 1 microM) did not have any effects on the promoter activity (106+/-5.7% after 0.1 microM angiotensin II stimulation) in Y1 cells and cultured vascular smooth muscle cells, although phorbol myristate acetate (PMA) decreased the promoter activity by about 40% compared with control. These results suggest that angiotensin AT1 receptor gene expression in the rat adrenal gland is inhibited by angiotensin II and it may not be due to suppression of promoter activity. Other mechanisms such as destabilization of angiotensin AT1 receptor mRNA or angiotensin II-induced increased blood pressure may be involved in the inhibition.
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PMID:Inhibition of the expression of the gene for the angiotensin AT1 receptor by angiotensin II in the rat adrenal gland. 968 24

The binding of 125I-labeled [Sar1,Ile8]angiotensin II to the hypothalamic membranes of the normotensive Wistar-Kyoto rat (WKY) and the spontaneously hypertensive rat (SHR) was studied. Displacement experiments with four centrally active angiotensins, losartan, and PD-123319 confirm the known existence of angiotensin AT1 and AT2 receptors in the rat hypothalamus. The values of the inhibitory constants for angiotensin II and PD-123319 in the SHR were significantly lower than the corresponding values in the WKY, indicating the possible existence of high-affinity hypothalamic AT1 and AT2 receptors for the two ligands in the SHR. The angiotensin AT1 receptor was further separated into a 5'-guanylyl imidodiphosphate-sensitive and -nonsensitive subtype, indicating that one of the subtypes is G protein coupled. The SHR has significantly higher numbers of measurable AT1-receptor subtypes as well as AT2 receptor subtypes. The former data support the findings of other investigators showing that the hypothalamus of the SHR expressed more AT1A and AT1B mRNAs than that of the normotensive rat. Des-Asp1-angiotensin I, which is known to attenuate the central pressor action of angiotensin II and angiotensin III, acts on both the AT1 and AT2 receptors, although it has a higher affinity for the AT1 receptors. The overall increase in the number of AT1 and AT2 receptors in the SHR is in line with the contention that the brain of the hypertensive rat, compared with that of the WKY, has a hyperactive renin-angiotensin system.
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PMID:Hypothalamic angiotensin receptor subtypes in normotensive and hypertensive rats. 968 61

Angiotensin II (AngII), a circulating vasoactive peptide, interacts with specific membrane-bound receptors on the target tissues (vessels, kidneys and adrenal gland). Using new pharmacological tools and molecular cloning, these receptors have been classified in two types, called AT1 et AT2, whereas two subtypes, called AT1A et AT1B, have been identified for the rodent AT1 receptors, but not in humans. All these receptors present a seven hydrophobic transmembrane domain structure, which is classical for G protein coupled receptors. The interspecies molecular homology of these AngII receptors is high (> 90 per cent identity) within the same type of receptor, but is rather low (approximately 35 per cent identity) between the two types of receptors. The AT1 receptors are responsible for most of the AngII physiological actions and are coupled to a Gq protein, which activates a phospholipase C producing second messengers which activate protein kinases C and mobilize calcium intracellular stores. More recently, a strong interaction of this receptor has been demonstrated with the signalling pathways of the tyrosine kinases. The molecular mechanisms and the physiological importance of these interactions remain to be elucidated. The intracellular signalling (Gi coupling and tyrosine phosphatase activation) and the physiological actions (cellular differentiation, apoptosis) of the AT2 receptors are more controversial.
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PMID:[Angiotensin II receptors: classification, structure, and signal transduction]. 977 19

The well known diversity of angiotensin II (AngII) action is due to the diversity of its receptors and subsequent intracellular signaling initiated by them. Both type 1 and 2 receptors (AT1 and AT2) were expression-cloned from various species. AT1 was shown to consist of two isoforms (AT1A and AT1B) in rodents, whereas only one AT1 was found in higher mammals. Most of the functions hitherto identified with AngII were due to AT1, but diverse functions are also being identified with AT2. Although AT1 and AT2 are both G protein-coupled receptors, their signals seem to result in opposite effects. For example, AT1 causes vascular growth by activating epidermal growth factor receptors and other tyrosine kinase systems, whereas AT2 seems to activate dephosphorylating enzymes, which in extreme situations lead to apoptosis. Results of studies with AT1A null mice or ATA X AT1B dual null mice and AT2-deleted animals indicate that AT2 works in the direction of vasorelaxation as opposed to vasoconstriction by AT1. Although AT1 works mainly through Gq/11 proteins, it has been shown that AT2 binds Gialpha2 and Gialpha3. However, the exact mechanisms of these actions are not clear and much work is required in many areas.
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PMID:Molecular biology and signaling of angiotensin receptors: an overview. 989 33

Mesangial cells are one of the main targets of angiotensin II (AngII) in the renal cortex. AngII receptors on mesangial cells are of high affinity (nanomolar range). They belong to the AT1 subtype as shown by the inhibitory effect of AT1 antagonists on [125I]-Sar1, Ala8 AngII binding and on all of the biologic effects mediated by AngII, such as cytosolic calcium stimulation, inositol phosphate formation, prostaglandin production, and cell contraction. AngII also exerts long-term effects on mesangial cells, including stimulation of cell growth and synthesis of a variety of proteins, essentially the components of the extracellular matrix (collagen, fibronectin) and the type 1 inhibitor of plasminogen activator. These effects are mediated, at least in part, by autocrine products, in particular endothelin, platelet-derived growth factor, and transforming growth factor-beta, whose synthesis is enhanced by AngII. Treatment by an AT1 receptor blocker of mice with experimental nephritis inhibits activation of type I collagen alpha2 chain promoter and prevents the development of glomerulosclerosis. AngII receptors in rat mesangial cells are equally distributed between the AT1A and AT1B isoforms. Treatment of these cells by AngII or losartan, an AT1 receptor blocker, has no effect on AT1A and AT1B receptor mRNA expression, whereas candesartan, another AT1 receptor blocker, increases and dexamethasone decreases this expression.
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PMID:Mesangial AT1 receptors: expression, signaling, and regulation. 989 39

This study determined the inhibitory effect of the angiotensin II (AngII) type I (AT1) receptor blocker candesartan on renal vascular reactivity in vivo. Reactivity to AngII before and during candesartan administration was assessed by measuring (by electromagnetic or ultrasonic flowmetry) renal blood flow responses to AngII in rats and mice. AngII produced greater renal vasoconstriction in 7-wk-old, spontaneously hypertensive rats than in Wistar-Kyoto rats. After indomethacin treatment, AngII (2 ng) produced 40% reductions in renal blood flow in both rat strains, without affecting systemic arterial pressure. Coadministration of candesartan blocked AngII effects in a dose-dependent manner, with similar levels of inhibition in spontaneously hypertensive rats and Wistar-Kyoto rats; maximal inhibition was 80%. In rats that had been pretreated (for 30 min) with intravenous candesartan, AngII-induced renal vasoconstriction was inhibited dose dependently up to 98%. To evaluate receptor subtype mediation, responses were compared in mice with or without the AT1A receptor (deleted by gene targeting). Intrarenal AngII (1 ng) caused a 32% reduction of renal blood flow in wild-type mice and an 8% reduction of renal blood flow in AT1A receptor-knockout mice. Ten nanograms of AngII were required to elicit 20% renal vasoconstriction in these mutant mice. Concurrent injection of candesartan caused dose-dependent inhibition of AngII up to 80%. The candesartan IC50 values for percentage changes in renal blood flow did not differ in the two groups of mice. These studies establish that candesartan is an effective, highly selective, AT1 receptor blocker, inhibiting renal vasoconstriction in rodents in a concentration- and time-dependent manner. Candesartan effectively blocks AT1A and AT1B receptors in renal resistance vessels of rodents, with similar efficacies in rats and mice.
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PMID:Effects of candesartan on angiotensin II-induced renal vasoconstriction in rats and mice. 989 64

We investigated the effects of the angiotensin II (Ang II) type 1 receptor (AT1) antagonist KRH-594 on levels of the mRNAs for AT1A, AT1B, platelet-derived growth factor-receptor beta (PDGF-Rbeta), and extracellular matrix (ECM)-related genes using the competitive reverse transcription-polymerase chain reaction (RT-PCR) method and on neointimal formation in the balloon-injured rat carotid artery. The mRNA levels for AT1A and PDGF-Rbeta, but not for AT1B, increased from day 3 after injury to day 14. KRH-594 administered orally at 3 and 10 mg/kg/day significantly suppressed these increases. KRH-594 (10 mg/kg/day) also suppressed the injury-induced gene expressions for transforming growth factor-beta1 and fibronectin and reduced collagen alpha1(I) and alpha1(III) mRNA levels for the first 7 days after injury. KRH-594 (10 and 30 mg/kg/day) significantly and dose-dependently reduced the neointimal area in cross sections of the artery 14 days after injury. Another AT1 antagonist, TCV-116 (candesartan cilexetil; 1 and 3 mg/kg/day p.o.), had similar effects on the morphological change and AT1A mRNA level, whereas a smooth muscle relaxant, hydralazine (10 mg/kg/day p.o.), did not. These results indicate that up-regulation of AT1A, PDGF-Rbeta, and ECM-related genes in the balloon-injured carotid artery is in part an AT1-mediated phenomenon and that prevention of receptor up-regulation may contribute to the attenuating effects of AT1 antagonists on neointimal formation after injury.
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PMID:Angiotensin II type 1 receptor blockade prevents up-regulation of angiotensin II type 1A receptors in rat injured artery. 991 4

ANG II contributes importantly to the regulation of renal vascular resistance, glomerular filtration, and tubular epithelial transport, yet there remains a paucity of information regarding the localization of the ANG II type 1 and 2 (AT1 and AT2) receptors within the rat kidney particularly within the vasculature. The present study was designed to localize the transcriptional and translational site(s) of AT1 and AT2 receptor (AT1R and AT2R, respectively) expression within the rat kidney. Using immunohistochemistry, we detected the AT(1)R translational sites throughout the kidney, with the strongest labeling found in the vasculature of the renal cortex and the proximal tubules of the outer medulla. The AT2R protein expression was found throughout the rat kidney, although there was little to no expression found in the glomerulus and medullary thick ascending limbs of Henle (TAL). Gene-specific primers were then designed to distinguish between the receptor subtypes within microdissected renal tubular and vascular segments using RT-PCR. AT1AR, AT1BR, and AT2R mRNA were found within the renal vasculature (afferent arterioles, arcuate artery, and outer medullary descending vasa recta). The mRNA for both the AT1R isoforms was also detected in the glomeruli and the renal tubules (proximal tubules, TAL, and collecting ducts); however, no AT2R mRNA was detected within the glomerulus and was inconsistently found within the medullary TAL (MTAL). Taken together, these data show that mRNA for the AT1R subtypes was located in all of the renal tubular and vascular segments. Evidence for AT2R mRNA was also found in all but two of the vascular and tubular segments, the MTAL, and the glomeruli. These results are consistent with the whole tissue immunohistochemically localized receptors.
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PMID:Distribution of angiotensin AT1 and AT2 receptor subtypes in the rat kidney. 1048 27

In addition to its function as a peripheral hormone, angiotensin II (AngII) has been shown to act as a neuromodulator in various brain regions. AngII effects are mediated by two major AngII receptor subtypes, AT1 and AT2, and different AT1 receptor isoforms AT1A and AT1B are described in rat brains. The purpose of the present study was to analyse the expression pattern of AT receptors in different parts of the rat eye with special emphasis on the retina. Specific primers were constructed and the gene expression of AngII receptor subtypes was investigated by means of reverse transcription-polymerase chain reaction (RT-PCR). An antibody was used for cellular localization of AT1 receptor in the retina. AT2 receptor mRNA was localized by in situ hybridization (ISH). We examined the retinas of different developmental stages as well as non-neuronal ocular tissues, e.g. choroid and anterior uveal tract of rats (Brown Norway and Wistar strain), for the gene expression of AT receptors. Our results show that AT1A and AT2 mRNAs are expressed in rat choroid, iris/ciliary body and retinas, whereas AT1B mRNA is not expressed in the retina but in all other ocular tissues under investigation. AT1 receptor immunohistochemistry of the retina showed strong labelling in the ganglion cell layer (GCL), and some cells in the inner nuclear layer (INL), suggesting putative ganglion cell but also amacrine cell labelling. In the retina, ISH for AT2 mRNA revealed labelling in the GCL and a faint labelling in the inner nuclear layer. No AT2 ISH-signal was found in the other ocular tissues. These data suggest that there is a specific distribution pattern of AT receptors in rat ocular tissues, especially in the retina. The expression of AT receptors on retinal ganglion cells confirms the AngII action on these cell types and supports the role of AngII as a retinal neurotransmitter or neuromodulator.
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PMID:Angiotensin II receptor subtype gene expression and cellular localization in the retina and non-neuronal ocular tissues of the rat. 1056 46

In mammalian brain, angiotensin II AT1 and AT2 receptor subtypes are apparently expressed only in neurons and not in glia. AT1 and AT2 receptor subtypes are sometimes closely associated, but apparently expressed in different neurons. Brain AT1/AT2 interactions may occur in selective cases as inter-neuron cross talk. There are two AT1 isoforms in rodents. AT1A, which predominates, and AT1B. There are also important inter-species differences in receptor expression. Relative lack of amino acid conservation in the gerbil gAT1A receptor substantially decreases affinity for the AT1 antagonists. AT1 receptors are expressed in brain areas regulating autonomic and hormonal responses. AT1A receptors are heterogeneously regulated in a number of experimental conditions. In specific areas, AT1A receptors are not normally expressed, but are induced under influence of reproductive hormones in dopaminergic neurons. There are AT1 and AT2 receptors also in areas related to limbic, sensory and motor functions and their expression is developmentally regulated. A picture is emerging of widespread, neuronally localized, heterogeneously regulated, closely associated brain angiotensin receptor subtypes, modulating multiple functions including neuroendocrine and autonomic responses, stress, cerebrovascular flow, and perhaps brain maturation, neuronal plasticity, memory and behavior.
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PMID:Emerging features of brain angiotensin receptors. 1058 48


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