UMLS:C0004135 - FACTA Search

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13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study describes methodology and its application to evaluate renal reactivity in acute studies on anesthetized mice. Renal blood flow (RBF) was measured using an ultrasonic transit-time flowmeter and a non-cannulating V-shaped probe. An intrarenal artery injection technique established feasibility and reproducibility of studies of renal vascular reactivity to angiotensin II (AngII) in adult wild-type mice. The study also examined whether AngII would affect RBF in mice lacking AT1A receptors due to gene targeting. Mean arterial pressure averaged 83 and 62 mmHg, respectively, in mice with and without AT1A receptors. The RBF was similar in both groups, averaging 7 ml/min per g kidney wt. AngII injection (10-microl bolus) into the renal artery produced transient, dose-dependent, selective reductions in RBF in AT1A knockout mice as well as wild-type mice. The response was considerably greater in mice with AT1A receptors: 10% for 0.1 ng, 30% for 1 ng, and 45% for 5 ng AngII in control animals versus respective decreases of 6, 15, and 17% in knockout mice. In other studies, angiotensin-converting enzyme (captopril) or renin (CP-71362-14) was inhibited. During inhibition of AngII formation, renal vascular reactivity to AngII increased twofold in both groups. Coadministration of the AT1 receptor antagonist losartan (1 to 1000 ng) elicited dose-dependent inhibition of AngII effects, with near maximum blockage of 80 to 90% in both groups of mice. The putative AT2 receptor antagonist PD 123319 inhibited 30 to 40% of AngII-induced vasoconstriction, whereas CGP 42112 had no effect in either group. In conclusion, AngII can elicit renal vasoconstriction, albeit attenuated, in AT1A knockout mice. The weaker RBF effects are most likely due to the absence of the AT1A receptor. Inhibition of the response by AT1 receptor antagonist suggests mediation by the AT1B receptor in these animals. The residual constrictor effect observed during AT1 receptor blockade and sensitive to PD 123319 appears to be mediated by a non-AT1 receptor.
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PMID:Renal vascular reactivity in mice: AngII-induced vasoconstriction in AT1A receptor null mice. 1058 3

In vitro receptor autoradiography was performed on rat brain and kidney sections stored frozen at -20 degrees C for extended time periods (17, 40, 64, 121, 183, 251, and 333 days). The results indicate that prolonged tissue storage has a differential effect upon 125I sar1ile8 angiotensin II binding to AT1 and AT2 receptor sites. Binding at AT1 receptor rich tissues studied (renal medulla, renal cortex, anterior pituitary, ventral hippocampus, spinal trigeminal nucleus, and nucleus of the solitary tract) shows a first order exponential decay pattern. The logarithmic linear regression slope (log(e) specific binding versus time), is significantly different from zero (p<0.05) in all AT1 rich tissues except for nucleus of the solitary tract (p=0.086). There is no detected loss of 125I sar1ile8 angiotensin II binding at the AT2 prominent regions in the superior colliculus, medial geniculate nucleus, and the inferior olivary nucleus. The half lives of AT1 receptors are highly variable, ranging from 36 days in the anterior pituitary to 442 days in the nucleus of the solitary tract, and this might be related to variable stability of AT1A and AT1B receptors. These observations should be taken into account when assessing and comparing AT1 and AT2 receptor subtype densities.
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PMID:Differential loss in function of angiotensin II receptor subtypes during tissue storage. 1079 4

The presence of the angiotensin AT1A-like receptor subtype in the pulmonary artery and AT1B-like receptor subtype in the pulmonary trunk of the rabbit has been reported in two earlier studies. The present study further investigated these receptor subtypes using five other angiotensins (namely angiotensin II, angiotensin III, angiotensin IV, angiotensin-(1-7) and angiotensin-(4-8)). The direct action of the angiotensins on the rabbit pulmonary arterial and trunk sections and the ability of each angiotensin to further contract or relax preconstricted sections of the pulmonary artery and trunk were studied using the organ bath set-up. The effects of angiotensin III on the 3H overflow from re-uptaken [3H]noradrenaline in the electrically-contracted rabbit pulmonary arterial and trunk sections were also studied. The contractile response of the arterial and trunk section had the following rank order potency: angiotensin II > angiotensin III > angiotensin IV. The contractile response to these angiotensins was greatly reduced or absent in the pulmonary trunk. Angiotensin II further contracted the preconstricted arterial and trunk sections. In contrast, angiotensin III further contracted the preconstricted arterial section but relaxed the preconstricted trunk section. Angiotensin IV similarly relaxed the preconstricted trunk section but had minimum effect on the preconstricted arterial section. Angiotensin-(1-7) and angiotensin-(4-8) had no effect on both sections. The actions of the three angiotensins were inhibited by losartan, an AT1-selective antagonist. Indomethacin, a cyclo-oxygenase inhibitor, inhibited the relaxation caused by angiotensin III and angiotensin IV in the trunk section. The effects of angiotensin III on the electrically preconstricted sections of the pulmonary trunk and artery were not accompanied by any significant changes in 3H overflow. The differential responses produced by angiotensin II and its immediate metabolites via two positionally located and functionally opposing receptor subtypes suggest that the pulmonary trunk and artery is not a passive conduit but an important regulator of blood flow from the heart to the lung.
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PMID:Actions of angiotensin peptides on the rabbit pulmonary artery. 1080 81

The interaction of ANG II with intrarenal AT1 receptors has been implicated in the progression of diabetic nephropathy, but the role of intrarenal AT2 receptors is unknown. The present studies determined the effect of early diabetes on components of the glomerular renin-angiotensin system and on expression of kidney AT2 receptors. Three groups of rats were studied after 2 wk: 1) control (C), 2) streptozotocin (STZ)-induced diabetic (D), and 3) STZ-induced diabetic with insulin implant (D+I), to maintain normoglycemia. By competitive RT-PCR, early diabetes had no significant effect on glomerular mRNA expression for renin, angiotensinogen, or angiotensin-converting enzyme (ACE). In isolated glomeruli, nonglycosylated (41-kDa) AT1 receptor protein expression (AT1A and AT1B) was increased in D rats, with no change in glycosylated (53-kDa) AT1 receptor protein or in AT1 receptor mRNA. By contrast, STZ diabetes caused a significant decrease in glomerular AT2 receptor protein expression (47.0 +/- 6.5% of C; P < 0.001; n = 6), with partial reversal in D+I rats. In normal rat kidney, AT2 receptor immunostaining was localized to glomerular endothelial cells and tubular epithelial cells in the cortex, interstitial, and tubular cells in the outer medulla, and inner medullary collecting duct cells. STZ diabetes caused a significant decrease in AT2 receptor immunostaining in all kidney regions, an effect partially reversed in D+I rats. In summary, early diabetes has no effect on glomerular mRNA expression for renin, angiotensinogen, or ACE. AT2 receptors are present in glomeruli and are downregulated in early diabetes, as are all kidney AT2 receptors. Our data suggest that alterations in the balance of kidney AT1 and AT2 receptor expression may contribute to ANG II-mediated glomerular injury in progressive diabetic nephropathy.
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PMID:Early streptozotocin-diabetes mellitus downregulates rat kidney AT2 receptors. 1120 1

Angiotensin II (Ang II) is a potent vasoactive peptide and displays growth factor-like properties. Different high-affinity Ang II receptor subtypes (AT1A, AT1B and AT2) have been cloned. They are expressed in various brain structures. Additionally, it has been assumed that Mas could interact directly or indirectly with the renin-angiotensin system. The AT1 receptor mediates pressor and mitogenic effects of Ang II, whereas physiological function and signaling mechanisms of the AT2 receptor remain poorly understood. Recent reports have shown that Ang II could mediate apoptosis through AT2 receptors. Since the AT1A, AT2 and Mas knockout mice provide new tools for uncovering potential actions of Ang II, the cell number in different brain structures of male adult wild-type mice and mice deficient for AT1A, AT2 or Mas was evaluated to get more insight into the role of Ang II in central nervous system development. In nearly all investigated brain structures (cortex, hippocampus, amygdala, thalamus), the cell number was significantly higher in AT2-deficient mice in comparison to wild-type mice. To the contrary, in AT1A-deficient mice the cell number was significantly less than in controls in the lateral geniculate and the medial amygdaloid nucleus. However, cell numbers were not changed in Mas-knockout mice compared to their wild-types. These results show the contrary effects of both angiotensin receptors on cell growth and represent the first demonstration of their action on neuronal cell development evidenced in the adult mouse brain.
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PMID:Genetic deletion of angiotensin AT2 receptor leads to increased cell numbers in different brain structures of mice. 1138 84

Accumulating evidence suggests that angiotensin II (ANG II) plays an important role in the complex affair of renal organogenesis. The renin-angiotensin system (RAS) is up-regulated during renal development and in the perinatal period. On the other hand, inhibition of the RAS, for example by angiotensin-converting enzyme (ACE) inhibitors, may produce specific renal abnormalities including abnormal renal vessels, failure to develop a renal pelvis and tubular atrophy associated with expansion of the interstitium. AT2 receptors are expressed abundantly during fetal development and are down-regulated markedly after birth, whereas the abundance of AT1 receptors increases as maturation proceeds. Mice with targeted deletions of genes for angiotensinogen or ACE revealed severe renal abnormalities. In contrast, AT1A, AT1B and AT2 receptor knockout animals exhibited milder abnormalities of the kidney. These findings suggest that AT1 and AT2 receptors are both involved in the development of the nephron, and that ANG II provides signals through both receptors. ANG II exerts in vitro growth-stimulatory effects on tubular cells. Moreover, ANG II induces synthesis of collagen type IV in tubular cells, a necessary prerequisite for successful basement membrane formation. These effects are mediated through AT1 receptors. Thus, it is feasible that blockade of the RAS during kidney organogenesis leads to a decrease in the growth factor ANG II that may be pivotal for tubular growth and differentiation. On the other hand, ANG II's growth-stimulatory effects through AT1 receptors may be counterbalanced by AT2 receptor-mediated apoptosis and growth inhibition. Therefore, alterations in AT2 receptor signalling may alter the delicate balance between growth stimulation and inhibition, leading to alterations in tubular formation.
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PMID:Angiotensin II and tubular development. 1238 87

We studied the binding properties of KRH-594, a new selective antagonist of angiotensin II (AII) type 1 (AT1) receptors, to rat liver membranes and to recombinant AT1 and AT2 receptors. Preincubation of rat liver membranes with KRH-594 produced maximal inhibition of [125I]-AII binding when the preincubation time was 1-2 h. Preincubation with KRH-594 for 2 h decreased the B(max) value and increased the Kd value. For human AT1, human AT2, rat AT1A and rat AT1B receptors, the Ki values for KRH-594 were 1.24, 9360, 0.67, and 1.02 nm, respectively. The rank order of K1 values for human AT1 receptors was KRH-594 >> EXP3174 > candesartan = AII. The order of specificities for human AT1 and AT2 receptors was candesartan > EXP3174 > KRH-594. Although a 2-h preincubation of human AT2 receptors with KRH-594 (30 microM) or CGP 42112 (a selective AT2 receptor antagonist; 0.3 nM) inhibited binding of [125I]-AII, the suppression by KRH-594 was not significant. These results indicate that KRH-594 binds potently to AT1 receptors in an insurmountable manner, and that at a very high dose (30 microM) it may also bind to AT2 receptors, but in a surmountable manner.
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PMID:Binding of KRH-594, an antagonist of the angiotensin II type 1 receptor, to cloned human and rat angiotensin II receptors. 1257 21

The renin-angiotensin (ANG) system has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). Because SHR are more susceptible to stress than normotensive Wistar-Kyoto rats (WKY), we measured the mRNA expression of AT1A, AT1B, and AT2 receptors in the hypothalamo-pituitary-adrenal (stress) axis of male SHR in comparison to age-matched WKY at prehypertensive (3 to 4 weeks), developing (7 to 8 weeks), and established (12 to 13 weeks) stages of hypertension. AT1A receptor mRNA was mainly expressed in the hypothalamus and adrenal gland. AT1B receptor mRNA was detected in the pituitary and adrenal gland. AT2 receptor mRNA was prominent only in the adrenal gland. When compared with WKY, SHR showed increased AT1A receptor mRNA levels in the pituitary gland at all ages in contrast to reduced pituitary AT1B receptor mRNA levels. In the adrenal gland of SHR, AT1B receptor mRNA levels were decreased at the hypertensive stages when compared with WKY. The reduced expression of adrenal AT1B receptor mRNA was localized selectively in the zona glomerulosa by in situ hybridization. No differences were observed between WKY and SHR in the expression of hypothalamic ANG receptors. ANG significantly increased plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone in dexamethasone-treated SHR but not in WKY. The aldosterone response to ANG was similar in SHR and WKY. Our results suggest a differential gene expression of AT1A and AT1B receptors in the hypothalamo-pituitary-adrenal axis of SHR and normotensive WKY and imply the participation of AT1 receptors in an exaggerated endocrine stress response of SHR to ANG.
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PMID:Differential expression of AT1 receptors in the pituitary and adrenal gland of SHR and WKY. 1289 May 82

In this study, the mouse neuroblastoma cell line Neuro-2a was analyzed for expression of angiotensin II receptors. Reverse-transcriptase polymerase chain reaction (RT-PCR) showed that Neuro-2a cells express mRNA of angiotensin II (AngII) receptor subtypes AT1A, AT1B, and AT2. Analysis of Neuro-2a cells by Western blotting revealed AT1 and AT2 receptor protein expression. The predominant molecular weights were determined to be 50.4 kDa for the AT1 receptor and 62.4 kDa for the AT2 receptor. Observation of AT1 and AT2 receptor localization within Neuro-2a cells using immunocytochemistry showed distribution similar to other G-protein coupled receptors with diffuse distribution in the cytosol, perinuclear enrichment and accumulation of receptors on the outer cellular periphery with extension into the neurites. Furthermore, we observed InsP3 formation following AngII induction that could be abolished in presence of the AT1A receptor antagonist losartan. The results clearly show expression of the AngII receptor types AT1A and AT2 in the Neuro-2a cell line. We conclude that Neuro-2a cells represent an interesting model cell line for study of mechanisms that control the interplay between these receptors.
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PMID:Angiotensin II receptor types 1A, 1B, and 2 in murine neuroblastoma Neuro-2a cells. 1268 May 93

ANG II controls the vascular tone of pre- and postglomerular arterioles, and thereby glomerular filtration, through binding to either AT1A, AT1B, or AT2 receptors. AT1 receptors, which are coupled to intracellular Ca2+ signaling, have vasoconstricting effects, whereas AT2 receptors, whose signaling mechanism is unknown, induce vasodilatation. The angiotensin receptors have been characterized in afferent arterioles, which express the three types of receptors, but not in efferent arterioles. Two subpopulations of juxtamedullary efferent arterioles, muscular ones which terminate as vasa rectae and thin ones which terminate as peritubular capillaries, have been described. They display functional heterogeneity with regard to the ANG II response. To evaluate whether these differences are associated with differential expression of ANG II receptors, we examined the expression pattern of AT1A, AT1B, and AT2 receptor mRNAs by RT-PCR in these arterioles and studied the effect of valsartan, a specific AT1-receptor antagonist. Results indicate that muscular arterioles express AT1A, AT1B, and AT2 receptors, whereas thin arterioles only express the AT1A and AT2 types, and at a much lower level. Valsartan fully inhibited ANG II-induced increases in intracellular Ca2+ in both arteriolar types, but with different kinetics. In muscular arterioles, inhibition was monoexponential, whereas it displayed a marked positive cooperativity in thin arterioles. Finally, the apparent affinity for valsartan was higher in muscular than in thin arterioles. In conclusion, this study further documents the differences between muscular and thin efferent arterioles with regard to ANG II signalization in the rat kidney.
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PMID:Angiotensin receptor subtypes in thin and muscular juxtamedullary efferent arterioles of rat kidney. 1273 2

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