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

The angiotensin II type 1 receptor (AT1R) in the central nervous system (CNS) plays a pivotal role in determining blood pressure. However, the relationship of the receptor to neurones in the spinal cord which are the final CNS contribution to sympathetic outflow is unknown. Here we first use RT-PCR to show that AT1A, AT1B and AT2 receptors are expressed in thoracic spinal cord of the rat. Using light microscopic immunohistochemistry we find that the AT1 receptor in the thoracic spinal cord is located on neurones and ependymal cells. Neurones with extensive immunostaining of somata and dendrites were located in the intermediolateral cell column (IML) and lamina X (the central autonomic area), regions associated with autonomic outflow, as well as in lamina V. Retrograde labelling and dual immunolabelling with nNOS revealed that those AT1R-immunopositive cells in the IML were sympathetic preganglionic neurones, while those in lamina X were unlikely to be. Punctate labelling resembling that of axonal fibres and terminals was evident in lamina II of the dorsal horn and throughout the cord. Electron microscopy in the IML and lamina X revealed that these puncta were presynaptic terminals, but also astrocyte processes. Immunolabelling was also evident beneath the plasma membrane in neuronal somata. These data show that the AT1R in the spinal cord is ideally located to influence autonomic outflow and hence participate in the CNS determination of blood pressure.
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PMID:Angiotensin type 1 receptor immunoreactivity in the thoracic spinal cord. 1295 65

Glomerular podocytes play a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by angiotensin II (Ang II) through activation of cell-surface receptors. Although studies suggest that podocytes express receptors for Ang II, the Ang II binding site has not been characterized with radioligand binding techniques. We therefore used iodine 125-labeled Ang II to monitor Ang II-receptor density during differentiation of a mouse podocyte cell line. Scatchard analyses of equilibrium binding data revealed a single class of high-affinity binding sites (dissociation constant approximately 3 nmol/L) in both differentiated and nondifferentiated cells. During differentiation, the density of Ang II-receptor sites increased roughly 15-fold in differentiated podocytes (maximal density of specific binding sites 881 fmol/mg protein) compared with that in nondifferentiated cells (52 fmol/mg protein; P<.005). Glomerular podocytes expressed messenger RNA for AT1A, AT1B, and AT2 receptor subtypes, and competitive binding studies found that differentiated podocytes expressed mostly AT1 receptors (approximately 75%) with lesser amounts of AT2 (approximately 25%). Up-regulation of Ang II-receptor number was associated with increased Ang II-receptor responsiveness, as evidenced by enhanced Ang II-stimulated inositol phosphate (IP) generation and incorporation of tritiated thymidine. Both [3H]thymidine incorporation and IP generation were mediated by AT1-receptor activation. These data suggest that glomerular podocytes express a high-affinity binding site for Ang II with pharmacologic characteristics of both AT1 and AT2 receptors. This receptor site is up-regulated during podocyte differentiation, and receptor activation induces both IP generation and DNA synthesis by AT1-dependent mechanisms. We speculate that activation of podocyte Ang II receptors contributes to glomerular damage in disease states.
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PMID:Characterization of angiotensin II-receptor subtypes in podocytes. 1464 35

Angiotensin (AT) II is known to enhance responses to electrical field stimulation (EFS) via AT1 receptors located on sympathetic nerve terminals. Differences in potency exist between AT1 receptor antagonists regarding the inhibition of the prejunctional and postjunctional AT1 receptors. It is hypothesized that prejunctional AT1 receptors might belong to the AT1B receptor subtype. Accordingly, the authors investigated whether AT1B receptor inhibition by high concentrations of PD123319 could suppress ATII-augmented noradrenergic transmission (prejunctional) in the rabbit thoracic aorta by means of a noradrenaline spillover model. Additionally, the influence of PD123319 on ATII-enhanced constrictor responses to electrical field stimulation was investigated in the isolated rabbit mesenteric artery. Furthermore, the authors investigated whether PD123319 could influence the constrictor responses (postjunctional) to ATII in both preparations. In the thoracic aorta, ATII (10 nM) caused a significant enhancement of EFS-evoked [3H]-noradrenaline release by a factor of 2.0 +/- 0.1. This reinforcement could be inhibited by PD123319 (0.1, 1, and 10 microM). The constrictor response to ATII was unaffected by PD123319. In the mesenteric artery, ATII (0.5 nM) caused a significant enhancement of constrictor responses to EFS by factors of 2.9 +/- 0.3, 2.3 +/- 0.3, and 1.6 +/- 0.1 at 1, 2, and 4 Hz, respectively. This enhancement could be attenuated by PD123319 (1 and 10 microM). The constrictor response to ATII was unaffected by PD123319. It is concluded that the prejunctional AT1 receptors belong to the AT1B subtype whereas postjunctional AT1 receptors do not.
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PMID:Different AT1 receptor subtypes at pre- and postjunctional sites: AT1A versus AT1B receptors. 1466 62

In the coarctation hypertension model, we showed both dissociation of plasma renin activity from cardiovascular-induced effects and the reversal of hypertension-induced responses by losartan. In this study, we investigated the effects of hypertension on the expression of brain renin-angiotensin system components and the simultaneous functional responses and effects of long-term angiotensin II (AT) receptor blockade on these responses. Rats were given vehicle or losartan for 9 days and subjected to subdiaphragmatic aortic constriction or sham surgery after 4 days of treatment. On the fifth postsurgical day, pressure and heart rate were measured in the conscious state; the brain was perfused and removed afterward. Sequential slices of brainstem were hybridized with 35S-oligodeoxynucleotide probes for angiotensinogen, AT1A, and AT1B receptors and processed for autoradiography and densitometry. In vehicle-treated rats, hypertension was accompanied by tachycardia and marked increments in angiotensinogen and AT1A mRNA expression in the cardiovascular system-controlling brainstem areas. In the nucleus tractus solitarii, AT1A density was correlated with both pressure and heart rate values (P<0.01), whereas angiotensinogen levels were correlated with pressure only (P<0.05). Losartan did not change the pressure of hypertensive rats (142+/-4 versus 146+/-2 mm Hg, losartan versus vehicle) and the hypertension-induced angiotensinogen mRNA expression but did block both tachycardic response and hypertension-induced AT1A mRNA expression. Hypertension and losartan did not change AT1B mRNA expression. The hypertension-induced positive feedback on angiotensinogen and AT1A mRNA expression supports the concept of a permissive role for brain angiotensin II in orchestrating circulatory responses during the development of hypertension. These data also explain the efficacy of long-term AT1 receptor blockade to reverse hypertension-induced effects.
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PMID:Endogenous angiotensin and pressure modulate brain angiotensinogen and AT1A mRNA expression. 1473 38

In experimental and human renal diseases, progression is limited by angiotensin-converting enzyme inhibitors. Whether renoprotection was due to their capacity of reducing proinflammatory and profibrotic effects of angiotensin II (Ang II) or limiting proteinuria and its long term toxicity is debated. For dissecting the relative contribution of Ang II and proteinuria to chronic renal damage, the protein-overload proteinuria model was used in genetically modified mice lacking the major isoform of murine AT1 receptor (AT1A). Uninephrectomized AT1A+/+ and -/- mice received a daily injection of BSA or saline for 4 or 11 wk. AT1A-/-BSA mice acquired a renal phenotype of proteinuria and renal glomerular and tubulointerstitial lesions, albeit attenuated with respect to AT1A+/+BSA. Administration of the calcium channel blocker lacidipine to reduce BP of AT1A+/+BSA mice to levels of AT1A-/-BSA translated into comparable values of protein excretion rate and glomerular and tubulointerstitial injury in both strains. These results confirm that the toxic effect of protein trafficking on renal disease progression is not necessarily dependent on Ang II to the extent that targeted deletion of AT1A does not prevent disease progression. A role of Ang II via AT1B or AT2 receptors is still a possibility that cannot be ruled out by the present experimental approach. These findings provide a clear rationale for specifically targeting proteinuria in pharmacologic interventions of chronic nephropathies.
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PMID:Targeted deletion of angiotensin II type 1A receptor does not protect mice from progressive nephropathy of overload proteinuria. 1546 71

We studied renal AT1 and AT2 receptors in male, female, ovariectomized and ovariectomized-estrogen-treated Wistar-Hanover and Wistar-Kyoto rats. AT1 receptors and AT1A receptor mRNA predominated, with no significant differences between males and females. AT2 receptor expression was restricted in female rats to the capsule, the transition zone between outer and inner medulla, the endothelium lining the papilla, and arcuate arteries and veins. There were no AT2 receptors in male rats, while male mice express substantial numbers of estrogen-dependent AT2 receptors. Arcuate arteries and veins expressed AT1B mRNA in males and females, and AT2 mRNA in females only. AT1 receptor and AT2 receptor expression were estrogen-dependent, with increases in AT1 and AT2 receptor expression after estrogen treatment in ovariectomized rats. Estrogen treatment increased prostaglandin E2 (PGE2) and cGMP concentrations in the renal medulla, and eNOS expression in cortical arteries. In rodents, expression of renal Angiotensin II receptor types is estrogen-dependent, with significant species, strain and area differences. Our results support an important role for AT2 receptors in the regulation of renal function and in the protective effects of estrogen in the kidney.
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PMID:Estrogen upregulates renal angiotensin II AT1 and AT2 receptors in the rat. 1554 36

1. The renin-angiotensin system may be involved in the compensatory adaptations occurring after the reduction of renal mass and during the consecutive changes leading to chronic renal failure. We therefore investigated the regulation of angiotensin II receptors in two models of renal hypertrophy in the rat: hypertrophy following uninephrectomy (UNx) or subtotal nephrectomy (STNx). The level of angiotensin type 1 (AT1A-R and AT1B-R) and type 2 (AT2-R) receptor mRNA was quantified by competitive reverse transcription-polymerase chain reaction (RT-PCR) in specific renal zones and the intrarenal distribution of angiotensin II receptors was analysed by immunohistochemistry. 2. In the UNx rats, AT1-R mRNA expression was not modified in the cortex or in the inner stripe of the outer medulla of the residual kidney at any time after the surgery (1, 4 and 12 weeks). In contrast, AT1-R mRNA expression was significantly reduced in these zones in STNx rats (-33% and -40%, respectively). This downregulation was organ-specific, as AT1-R mRNA levels were not modified in the liver. The proportions of AT1-R subtype (AT1A and AT1B) mRNA were unchanged by UNx or STNx. Very low levels of AT2-R mRNA were found in the cortex of all groups. Immunostaining revealed a similar localization of AT1-R in mesangial cells, proximal tubule, basolateral membrane of thick ascending limb, in both models of hypertrophy. AT1-R labelling was also detected in the apical membrane of intercalated cells of cortical collecting ducts. 3. This differential mRNA expression of angiotensin II receptors during compensatory hypertrophy and renal injury suggests that the development of renal hypertrophy is independent of AT1-R and AT2-R gene expression levels.
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PMID:Differential regulation of angiotensin II receptors during renal injury and compensatory hypertrophy in the rat. 1581 Sep 86

Sarcosine1, glycine8 angiotensin II (SG Ang II) displayed unusual characteristics in early pharmacological studies. It was a potent antagonist of the dipsogenic actions of intracerebroventricularly administered Ang II in the rat, but showed low affinity for bovine cerebellar Ang II receptors. It has recently been shown that SG Ang II binds preferentially to the AT1 receptor. To determine if SG Ang II is a functional antagonist of the AT1 receptor-mediated calcium signaling, CHO cells stably transfected with AT1 receptors were exposed to Ang II in the presence and absence of SG Ang II. At concentrations of 10-100 nM, SG Ang II completely inhibited Ang II-stimulated intracellular Ca2+ mobilization in AT1A and AT1B receptor-transfected cells. SG Ang II and 125I- SG Ang II bound to AT1A and AT1B receptor-transfected cells with KD and KI values of 2-4 nM. In contrast, SG Ang II bound to AT2 transfected cells with a KI value of 7.86 microM. These results demonstrate that SG Ang II is a selective and functional peptide antagonist of the AT1 angiotensin II receptor subtype.
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PMID:Sarcosine1, glycine8 angiotensin II is a functional AT1 angiotensin receptor antagonist. 1588 19

Numerous studies have shown that angiotensin II causes vasoconstriction both by a direct action on smooth muscle cells (postjunctional effect) and indirectly through the facilitation of noradrenaline release from postganglionic sympathetic neurons (prejunctional effect). The receptors through which angiotensin II exerts its actions were first divided into AT1 and AT2 subtypes. A further subdivision of AT1 receptors into AT1A and AT1B subtypes was based on cloning and receptor binding studies: AT1A showed a high affinity for losartan, but low affinity for PD123319, while AT1B receptors showed nearly 100-fold lower affinity for losartan and 10,000-fold higher affinity for PD123319 relative to AT1 sites. The present review deals with functional evidence supporting the existence of AT1A and AT1B subtypes in the cardiovascular system. Taken together, all the functional results obtained in vivo and in vitro-in a wide variety of vascular tissues from different species-allow one to conclude that angiotensin II AT1 receptors are different pre- and postjunctionally and also that prejunctional and postjunctional angiotensin II receptors most probably belong to AT1B and AT1A subtypes, respectively.
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PMID:Functional evidence that in the cardiovascular system AT1 angiotensin II receptors are AT1B prejunctionally and AT1A postjunctionally. 1595 95

1. The differential identification of the angiotensin AT1A and AT1B receptor subtypes is impaired by the existing>96% homology of both receptors. In the present study, we characterized two polyclonal rabbit peptide antibodies, namely alpha-AT1A and alpha-AT1B, that recognize the C-terminal region of mouse AT1A and AT1B receptors, respectively. 2. In immunoblotting, both antibodies detected two major AT1 receptor-specific bands at sizes of 72.5 and 87.6 kDa in mouse tissues and in Neuro-2a cell lysates. In immunohistochemistry, antibodies demonstrated AT1 receptor-specific staining in renal proximal and distal tubules, as well as in kidney glomeruli. In addition, both antibodies stained AT1 receptors in Neuro-2a cells with G-protein receptor typical distribution. Dot-blot and ELISA analysis of the alpha-AT1A antibody showed 2.5- to fourfold higher selectivity for its AT1A receptor target peptide (1A-PEP) compared with the non-specific AT1B receptor peptide (1B-PEP). In contrast, the alpha-AT1B antibody showed high binding affinity towards its target peptide 1B-PEP, but also demonstrated high cross-reactivity for the non-specific peptide 1A-PEP (1.4- to twofold in ELISA and dot-blot analysis). In contrast with the lack of recognition by the alpha-AT1B antibody, the alpha-AT1A antibody selectively recognized the AT1A receptor fused to red fluorescence protein in transiently transfected Chinese hamster ovary cells. 3. In summary, we have generated two new peptide antibodies to the mouse AT1A and AT1B receptors (alpha-AT1A and alpha-AT1B), of which the alpha-AT1A antibody has the capability to distinguish AT1A receptor types in immunological approaches.
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PMID:Characterization of two polyclonal peptide antibodies that recognize the carboxy terminus of angiotensin II AT1A and AT1B receptors. 1640 50


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