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

The localization of two type 1 angiotensin II receptor subtype mRNA, AT1A and AT1B, was determined by reverse transcription-PCR on microdissected glomeruli and nephron segments. The coupling sensitivity of these two receptor subtypes was evaluated by measuring variations in intracellular calcium ([Ca2+]i) elicited by angiotensin II (Ang II) in structures expressing either AT1A or AT1B mRNA, using Fura-2 fluorescence. The highest expression of AT1 mRNA was found in glomerulus, proximal tubule, and thick ascending limb. In glomerulus, AT1A and AT1B mRNA were similarly expressed, whereas in all nephron segments AT1A mRNA expression was dominant (approximately 84%). The increase in [Ca2+]i elicited by 10(-7) mol/L Ang II was highest in proximal segments (delta [Ca2+]i is approximately equivalent to 300 to 400 nmol/L) and thick ascending limb (delta [Ca2+]i is approximately equivalent to 200 nmol/L). In glomerulus and collecting duct, the response was lower (delta < 100 nmol/L). The median effective concentrations for Ang II were of the same order of magnitude in glomerulus (12.2 nmol/L), in which both AT1A and AT1B are expressed, and in cortical thick ascending limb (10.3 nmol/ L), in which AT1A is almost exclusively expressed. The Ang II-induced calcium responses were totally abolished by the AT1 receptor antagonist losartan (1 mumol/L) but not by the AT2 antagonist PD 123319 (1 mumol/L). In the absence of external Ca2+, the peak phase of the response induced by 10(-7) mol/L Ang II was reduced and shortened, suggesting that a part of the [Ca2+]i increase originated from the mobilization of the intracellular Ca2+ pool. In conclusion, these results demonstrate that in the rat kidney: (1) AT1A is the predominant AT1 receptor subtype expressed in the nephron segments, (2) glomerulus is the only structure with a relatively high AT1B mRNA content, and (3) AT1A and AT1B receptor subtypes do not differ in their efficiency for the activation of calcium second-messenger system.
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PMID:Expression of type 1 angiotensin II receptor subtypes and angiotensin II-induced calcium mobilization along the rat nephron. 935 68

Using an in situ perfusion technique of isolated left rat adrenal gland, it has been demonstrated that angiotensin-II (ANG-II) increases DNA synthesis in the zona glomerulosa (ZG), but not fasciculata-reticularis cells. The AT1 receptor antagonist DuP753 abolished the effect of ANG-II, while the AT2 receptor antagonist PD 123319 potentiated it. Both Ro31-8220, an inhibitor of protein kinase C (PKC), and tyrphostin-23, an inhibitor of tyrosine kinase (TK), evoked a partial reversal of ANG-II effect, and when added together to the perfusion medium abolished it. In contrast, the phospholipase C inhibitor U-73122 alone was able to induce a complete blockade of ANG-II effect. Neither the phospholipase A2 inhibitor AACOCF3 nor the cyclooxygenase inhibitor indomethacin and the lipoxygenase inhibitor phenidone affected ANG-II-induced stimulation of DNA synthesis, thereby making unlikely the involvement of the arachidonic acid signaling pathways. Our findings suggest that (i) ANG-II stimulates rat ZG cell proliferation acting via AT1 receptors coupled with phospholipase C, which activates both PKC and TK signaling systems; and (ii) the proliferogenic effect of ANG-II is partially counteracted by the activation of the AT2 receptor subtype.
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PMID:Angiotensin-II stimulates DNA synthesis in rat adrenal zona glomerulosa cells: receptor subtypes involved and possible signal transduction mechanism. 937 6

We studied the distribution of angiotensin II (AII) receptors type 1 (AT1) and type 2 (AT2) and the effects of a low sodium intake on these two subtypes of receptors in male rat adrenals. Binding studies on adrenal slices, on cell membranes and on cell suspensions were performed using [125I]AII and specific analogs for AT1 (Losartan) and AT2 (PD 123319) receptors. The distribution of AT1 was also studied by immunofluorescence. Complementary approaches were necessary to reach our goal. Indeed, by autoradiography on adrenal slices, [125I]AII was shown to bind to the zona glomerulosa (ZG) and to the medulla (M). When coincubated with [125I]AII, PD 123319 displaced [125I]AII from the medulla and from the ZG, indicating the presence of AT2 receptors in both zones. Losartan partially displaced [125I]AII from the ZG, indicating the presence of AT1 receptors in that zone. Furthermore, the labeling intensity of the medulla (AT2 receptors) was much stronger in adrenal sections from rats kept on a low sodium regimen than from controls. Immunofluorescence microscopy revealed that AT1 receptors were located mainly in the ZG of control rats. After sodium restriction, AT1 receptors appeared to be uniformly distributed within an enlarged ZG; furthermore AT1 receptor-positive cells were found to a limited degree in the zona fasciculata and possibly in the zona reticularis, and a greater number of these positive cells appeared in these zones under sodium restriction. Cell suspensions from rats fed a low sodium diet showed a 2.7- and 2.1-fold increase in total AII receptors in adrenal ZG and ZFR + M cells when compared with controls. Based on Losartan displacement, we calculated that [125I]AII bound to AT1 and to AT2 receptors was increased in both ZG and ZFR + M cell preparations under sodium restriction. Results of binding studies on cell membranes were also indicative of an increasing effect of sodium restriction on AT1 and AT2 receptors binding capacity. Furthermore, Northern blotting analysis revealed 3.0- and 2.5-fold increases in the level of AT1 receptor mRNA in the ZG and the ZFR + M of rats fed a low sodium diet as compared with those fed a normal diet. The low sodium intake resulted in a weaker increase (1.5-fold) in the level of AT2 receptor messenger RNA in the ZG, with no changes in the ZFR + M preparations. In conclusion, in this study complementary approaches were needed to determine the localization of AT1 and AT2 receptors in the rat adrenal, and to show the increasing effects of a low sodium regimen on the adrenal level of these receptors. Immunofluorescence studies revealed AT1 receptors mainly in the ZG and also in some cells of the inner adrenal cortex zones; in adrenals of rats kept on a low sodium diet the ZG was markedly enlarged, and an increased number of immunoreactive cells with AT1 receptors were observed throughout that zone; also more immunoreactive cells were present in the inner zones of the adrenal cortex. Furthermore in the adrenals of rats kept on a low sodium diet, we observed: 1) an increased number of AT1 and AT2 receptors in cell suspensions from the ZG, and in cell suspensions of the ZFR + M; 2) an increased level of AT1 and AT2 receptor mRNAs in the ZG; 3) an increased level of AT1 receptor mRNA, with no changes in the AT2 mRNA level in the ZFR + M. These results suggest a role for AT1 as well as for AT2 receptors in controlling adrenal function and differentiation under normal as well as under physiological stimulation of AII production following sodium restriction.
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PMID:Influence of dietary sodium restriction on angiotensin II receptors in rat adrenals. 938 7

The high abundance of angiotensin II (Ang II) AT2, relative to the AT1 receptor subtype in developing kidneys may be related to their potential as mediators of cell growth, although little evidence exists to support this concept. Renomedullary interstitial cells (RMICs) differentiate early in embryonic kidneys and are important in subsequent nephron development. These cells have been shown in vivo to possess AT2 binding sites, although the functional significance of these sites remains unknown. The aim of the current investigation was to examine the actions of Ang II on cultured embryonic renomedullary interstitial cells (ERMICs). 125I-[Sar1, Ile8]Ang II specifically bound to AT1 and AT2 receptors on ERMICs, and their mRNAs were detected by reverse transcription--polymerase chain reaction (RT-PCR). Angiotensin II (10(-6) M) increased intracellular IP3 concentrations at 20 seconds, and decreased intracellular cAMP concentrations after 10 minutes. Angiotensin II (10(-6) M) induced an increase in [3H]thymidine incorporation, mediated through the AT1 receptor subtype. Basic fibroblast growth factor (bFGF; 20 ng/ml) also increased 3[H]thymidine incorporation after 24 hours of treatment, an effect that was attenuated by subsequent addition of Ang II (10(-6) M). This antiproliferative action of Ang II was blocked by PD 123319 (10(-6) M), an AT2 receptor antagonist, and was not affected by losartan (10(-6) M), an AT1 receptor antagonist. These results indicate a dual role for Ang II in regulating ERMIC mitogenesis: a growth stimulating effect mediated by the AT1 receptor subtype, and an antiproliferative effect mediated by the AT2 receptor subtype.
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PMID:Angiotensin II inhibits growth of cultured embryonic renomedullary interstitial cells through the AT2 receptor. 945 4

In the present study we tested the hypothesis whether an angiotensin AT2 receptor-mediated stimulation of the bradykinin (BK)/nitric oxide (NO) system can account for the effects of AT1 receptor antagonism on aortic cGMP described previously in SHRSP. Adult SHRSP were treated for 4 hours with angiotensin II (ANG II) (30 ng/kg per min IV) or vehicle (0.9% NaCl I.V.). Animals were pretreated with vehicle, losartan (100 mg/kg P.O.), PD 123319 (30 mg/kg I.V.), losartan plus PD 123319, icatibant (500 microg/kg I.V.), N(G)-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg I.V.), or minoxidil (3 mg/kg I.V.). Mean arterial blood pressure (MAP) was continuously monitored over the 4-hour experimental period, and plasma ANG II and aortic cGMP were measured by RIA at the end of the study. ANG II infusion over 4 hours raised MAP by about 20 mm Hg. Losartan alone or losartan plus ANG II as well as minoxidil plus ANG II markedly reduced blood pressure when compared to vehicle-treated or ANG II-treated animals, respectively. Plasma levels of ANG II were increased 2-fold by ANG II infusion alone or by ANG II in combination with icatibant, L-NAME, or minoxidil. The increase in plasma ANG II levels was even more pronounced after losartan treatment. Aortic cGMP content was significantly increased by ANG II, losartan, losartan plus ANG II, and minoxidil plus ANG II by 60%, 45%, 68%, and 52%, respectively (P<.05). The effects of ANG II and of losartan plus ANG II on aortic cGMP content were both blocked by cotreatment with the AT2 receptor antagonist PD 123319. Icatibant and L-NAME abolished the effects of ANG II on aortic cGMP. Our results demonstrate the following: (1) ANG II increases aortic cGMP by an AT2 receptor-mediated action because the effect could be prevented by an AT2 receptor antagonist; (2) the effect of ANG II was not secondary to blood pressure increase because it remained under reduction of MAP with minoxidil; (3) losartan increased aortic cGMP most likely by increasing plasma ANG II levels with a subsequent stimulation of AT2 receptors; and (4) the effects of AT2 receptor stimulation are mediated by BK and, subsequently, NO because they were abolished by B2 receptor blockade as well as by NO synthase inhibition.
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PMID:AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. 945 27

Angiotensin II facilitates epinephrine release during insulin-induced hypoglycemia, and this effect appears to be independent of type 1 angiotensin II (AT1) receptors in man. In the present study, we hypothesized that the action of angiotensin II on adrenomedullary epinephrine release is mediated by an AT2 receptor-dependent mechanism. In conscious chronically instrumented rats, we measured plasma concentrations of catecholamines during acute insulin-induced hypoglycemia in groups of rats pretreated with the AT1 receptor antagonist losartan (10 mg/kg i.v.), the AT2 receptor antagonist PD123319 (30 mg/kg i.v.), combined losartan + PD123319, the converting enzyme inhibitor enalapril (1 mg/kg i.v.), or vehicle. In vehicle-treated rats, the area under the curve for changes in plasma epinephrine concentration [AUC(plasma epinephrine)] during insulin-induced hypoglycemia was 111+/-8 nmolXh/L (+/-SEM). Pretreatment with losartan alone did not affect AUC(plasma epinephrine) (113+/-17 nmol x h/L), while pretreatment with PD123319 tended to reduce the response (87+/-10 nmol x h/L; P=.08 versus vehicle). However, AUC(plasma epinephrine) was significantly reduced in rats that were pretreated with combined losartan + PD123319 (68+/-5 nmol x h/L; P<.001 versus vehicle) or enalapril: 86+/-10 nmol x h/L (P<.05 versus vehicle). Thus, combined treatment with losartan + PD 123319 proved more effective in attenuating the reflex increase in plasma epinephrine concentration during hypoglycemia than either of the two AT receptor antagonists given alone. We speculate that angiotensin II through binding to both receptor subtypes facilitates the sympathoadrenal reflex response by actions at several anatomical levels of the neural pathways involved in the sympathoadrenal reflex response elicited during insulin-induced hypoglycemia.
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PMID:AT1 and AT2 receptor blockade and epinephrine release during insulin-induced hypoglycemia. 945 33

Angiotensin II stimulates secretion of corticosteroids and an ouabain-like compound from adrenocortical cells. The angiotensin AT1 and AT2 receptor subtypes have been linked with stimulated secretion of aldosterone and endogenous ouabain, respectively, but the second messenger mechanisms involved in the latter secretion are not known. Accordingly, we investigated the effects of several pharmacological agents that affect signaling pathways on the basal and stimulated secretions of aldosterone and endogenous ouabain from primary cell cultures of bovine adrenocortical cells. The AT2 receptor antagonist, PD 123319, blocked the effects of angiotensin II on secretion of endogenous ouabain but not aldosterone. Treatment of the cells with either dibutyryl cAMP, a membrane permeant analog, or the phorbol ester tetradecanoyl phorbol acetate stimulated aldosterone secretion but had no effect on the secretion of endogenous ouabain. On the other hand, the membrane permeant analog, 8BcGMP, maximally activated secretion of endogenous ouabain whereas incubation of cells with sodium orthovanadate blocked angiotensin II stimulated secretion of endogenous ouabain. Neither 8BcGMP nor sodium orthovanadate affected the basal or stimulated components of aldosterone secretion. These results show that the secretions of aldosterone and endogenous ouabain from bovine adrenocortical cells are mediated by different intracellular signaling mechanisms and provide evidence that the adrenal secretions of these steroids are regulated differently.
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PMID:Different signaling pathways mediate stimulated secretions of endogenous ouabain and aldosterone from bovine adrenocortical cells. 945 46

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells and a vascular permeability factor. In this study we found that the addition of angiotensin II (AII) to rat heart endothelial cells induced VEGF mRNA production. VEGF mRNA levels reached a plateau within 2 h after the addition of AII and decreased after 4 h. The induction was superinduced by cycloheximide and blocked by actinomycin D. Losartan, an AT1 receptor antagonist, abolished the induction of VEGF mRNA by AII, whereas PD 123319, an AT2 receptor antagonist, had no effect on VEGF mRNA induction. H7, a protein kinase C inhibitor, blocked the induction. RT-PCR experiments showed two mRNA species (VEGF 120 and VEGF 164) in these cells and both species were stimulated by AII. Transient transfection experiment showed that VEGF promoter activity was increased 2.2-fold upon AII stimulation. Electrophoretic mobility shift assay revealed an enhanced binding of transcription factors AP-1 and NF-kappa B. Immunoblot analysis showed that the amount of secreted VEGF was elevated in the medium 8 h after AII stimulation. Our results demonstrate for the first time that the upregulation of VEGF by AII may play a significant role in AII-induced hyperpermeability.
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PMID:Upregulation of vascular endothelial growth factor by angiotensin II in rat heart endothelial cells. 953 74

1. Dahl Iwai salt-sensitive (DS) rats have been reported as becoming hypertensive with left ventricular hypertrophy (LVH) and heart failure when on a high-salt diet. Their circulating renin-angiotensin system (RAS) has been reported to be suppressed. To evaluate the role of angiotensin II (AngII) type 1 and type 2 receptors (AT1 and AT2, respectively) in LVH, we compared cardiac AT1 and AT2 receptors in 10-week-old DS rats and Dahl Iwai salt-resistant (DR) rats. 2. Seven pairs of 6-week-old male DS and DR rats were fed either a low- or high-salt diet (0.3 or 8% NaCl, respectively) for 4 weeks. Left ventricular AngII receptors were measured by radioligand binding assays using [125I]-[Sar1,Ile8]-AngII in plasma membrane fractions from these four groups. The AT1 and AT2 receptors were distinguished using their specific antagonists CV 11974 and PD 123319, respectively. 3. The high-salt diet increased blood pressure and the left ventricle:bodyweight ratio in DS rats. However, neither Bmax for AT1 and AT2 receptors nor Kd for [125I]-[Sar1,Ile8]-AngII differed between the groups. These results are different from those of other reports of pressure-overload LVH, such as spontaneously hypertensive rats or renovascular hypertension rats, in which AT1 and AT2 receptors were reported to be up-regulated.
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PMID:Angiotensin II receptors in cardiac left ventricles of Dahl rats. 959 May 78

The vertebrate renin-angiotensin system controls cardiovascular, renal and osmoregulatory functions. Angiotensin II (ANG II) is the most potent hormone of the RAS but in some vertebrate animals angiotensin III (Val4-ANG III) may be a hormone. We studied the effects of some angiotensins and mammalian ANG II receptor antagonists on nasal salt gland function and arterial blood pressure in conscious white Pekin ducks. Nasal salt gland fluid secretion (NFS) was induced by a 10 ml.kg-1 bw i.v. injection of a NaCl solution (1000 mosmol.kg-1 H2O) and maintained by a continuous i.v. infusion of the same solution at a rate of 0.97 ml.min-1. There was a positive linear correlation between nasal fluid [Na+] and osmolality, between [Na+] and [K+], and also between the rate of NFS and [Na+] and [K+]. [Asp1, Val5]-ANG II (1 nmol.kg-1 i.v.) inhibited NFS but did not change ionic concentrations. Val4-ANG III (1 or 5 nmol.kg-1) and ANG I (1-7) (20 nmol.kg-1) had no effect on NFS. [Sar1, Ile8]-ANG II (SARILE) acted as an ANG II receptor agonist and resulted in a prolonged and complete inhibition of NFS. The AT1 receptor antagonist, losartan (DuP 753) and the AT2 receptor antagonist, PD 123319 both failed to block the inhibitory effect of [Asp1, Val5]-ANG II on the nasal salt glands. [Asp1, Val5]-ANG II (2 nmol.kg-1 i.v.) increased mean arterial blood pressure (MABP), whereas the same dose of [Asn1, Val5]-ANG II (teleost) had only 30% of the pressor potency of the avian ANG II. Neither 1 nor 5 nmol.kg-1 of Val4-ANG III i.v. nor 20 nmol.kg-1 of ANG I (1-7) had any measurable effect on MABP. SARILE blocked completely the pressor response to [Asp1, Val5]-ANG II but the AT1 antagonists losartan and CGP 48933 and the AT2 antagonist PD 123319 all failed to block the pressor response to [Asp1, Val5]-ANG II. These results have substantiated an important role of the nasal salt gland in potassium regulation and highlighted a pharmacological dimorphism of saralasin, namely agonist and antagonist to angiotensin II-mediated inhibition of nasal salt gland function and pressor response, respectively. Using specific nonpeptidergic angiotensin II receptor antagonists, we have confirmed the distinct pharmacology of the avian angiotensin II receptors in a nongallinaceous species and the absence of significant angiotensin I (1-7) and angiotensin II effects on the cardiovascular system and nasal salt gland.
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PMID:Effects of ANG II and III and angiotensin receptor blockers on nasal salt gland secretion and arterial blood pressure in conscious Pekin ducks (Anas platyrhynchos). 959 62


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