UMLS:C0004135 - FACTA Search

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

The effect of angiotensin 1-7 (Ang 1-7) on the proximal tubule has not been well studied. It was hypothesized that Ang 1-7 has a biphasic effect on fluid absorption in the isolated rat proximal straight tubule. Proximal straight tubules were perfused at a rate of 5.81 +/- 0.44 nL/mm per minute and absorbed fluid at 0.98 +/- 0.10 nL/mm per minute. Bicarbonate absorption was 80.1 +/- 11.6 pmol/mm per minute. When 10(-12) M Ang 1-7 was added to the bath, fluid absorption increased to 1.47 +/- 0.10 nL/mm per minute (P < 0.013) and bicarbonate increased to 115.0 +/- 12.8 pmol/mm per minute (P < 0.004). Ang 1-7 had no effect on either the maximum rate of bicarbonate absorption (P > 0.90) or bicarbonate permeability (P > 0.60). Next, 10(-8) M Ang 1-7 was used. During the control period, fluid absorption was 0.90 +/- 0.09 nL/mm per minute. When 10(-8) M Ang 1-7 was added, fluid absorption decreased to 0.62 +/- 0.04 nL/mm per minute (P < 0.05). DuP 753, an AT1 receptor antagonist, blocked both effects induced by Ang 1-7, whereas PD 123319, an AT2 receptor antagonist, did not block the stimulatory effect. From these data, it was concluded that Ang 1-7 binds AT1 receptors and has a biphasic effect on fluid absorption, and at physiologic levels, the heptapeptide induces the stimulation of bicarbonate absorption.
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PMID:Angiotensin 1-7 has a biphasic effect on fluid absorption in the proximal straight tubule. 784 54

The effect of angiotensin II on rat cerebral arteries was studied using isolated, perfused segments of anterior cerebral arteries. The infusion rate was set to maintain baseline intraluminal pressure at 75 mmHg. Angiotensin II (100 nM) increased the intraluminal pressure by 22.5 +/- 2.2 mmHg. Losartan, an AT1 antagonist, at 1 microM, completely blocked the effect of angiotensin II, whereas the AT2 ligands PD 123319 (1 microM) and CGP 42112 (1 microM) were ineffective. None of these AT1 or AT2 selective ligands alone displayed any agonist effects. The results show that angiotensin II induces contraction of the rat anterior cerebral artery by acting on AT1 receptors.
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PMID:Angiotensin II AT1 receptor mediated contraction of the perfused rat cerebral artery. 788 Oct 45

Angiotensin II recognizes two receptor subtypes, AT1 and AT2, both of them having been recently cloned. Although AT2 receptors represent 5-10% of angiotensin II receptors in the kidneys of adult rats, their function remains unknown. In the present work, we examined the possible contribution of AT2 receptors to the regulation of pressure-natriuresis in anesthetized rats infused either with the specific AT2 antagonist PD 123319, or with CGP 42112B, an AT2 ligand with agonistic properties. The effects of PD 123319 were examined in a preparation with stable levels of angiotensin II, and in which AT1 receptors were blocked by the specific antagonist losartan. The effects of CGP 42112B were studied in rats deprived of endogenous angiotensin II. AT2 receptor blockade with PD 123319 did not change the renal blood flow while it increased the diuresis and natriuresis. These effects persisted even after full AT1 receptor blockade with losarfan. CGP 42112B did not modify the renal blood flow, but dose-dependently decreased urine flow and natriuresis. These results show that, contrary to AT1 receptors, renal AT2 receptors have no effect on total renal blood flow, but blunt the pressure-natriuresis, thus demonstrating that this receptor subtype is involved in a function of importance for body fluid and blood pressure regulation.
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PMID:Subtype 2 of angiotensin II receptors controls pressure-natriuresis in rats. 788 85

The rabbit proximal tubule (PT) has been widely utilized to study the direct effects of angiotensin II (ANG II) on PT function. The purpose of the present study was to characterize the binding properties of PT ANG II receptors, using nonpeptide antagonists, and to clone a rabbit PT ANG II receptor. In rat and rabbit kidney cortical brush-border and basolateral membranes, specific binding of 125I-ANG II was inhibited by the AT1 ANG II-receptor antagonist DuP 753, but not by the AT2 antagonist PD 123319. Using a rabbit kidney cortex cDNA library, we isolated cDNA encoding an ANG II receptor, with an open-reading frame sharing a high degree of sequence homology to previously cloned AT1 ANG II receptors. In transfected COS-1 cells, this rabbit ANG II receptor had properties of the AT1 class. Northern analysis revealed high levels of mRNA expression for this receptor in rabbit kidney cortex and adrenal gland. Within the kidney, message was detected in primary cultures of rabbit PT cells, as well as in freshly isolated rabbit PT segments. Message was also present in cells of the mouse PT line, MCT, and in rat glomerular mesangial cells. Utilizing polymerase chain reaction (PCR) with primers derived from the 1st and 4th transmembrane domains of the rat AT1A ANG II receptor, a 279-bp DNA fragment was amplified from reverse-transcribed RNA from rabbit PT cells. This DNA encoded an amino acid sequence identical to that encoded by the rabbit kidney cDNA clone in the corresponding region and differed by a single base substitution. Southern analysis of rabbit genomic DNA restriction digests with the rabbit ANG II receptor probe revealed hybridization to a single band in each lane. These results indicate that an AT1 ANG II receptor is present in the PT and that a single gene codes for the AT1 receptor in rabbit. The clone isolated in the present study should provide a useful tool with which to study the regulation of the PT renin-angiotensin system.
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PMID:Cloning of a rabbit kidney cortex AT1 angiotensin II receptor that is present in proximal tubule epithelium. 791 79

In previous studies, we found that central administration of the AT1-receptor antagonist, EXP 3174, and the AT2-receptor antagonist, PD 123319, blocked the cardiovascular response to centrally-injected angiotensin II (AII), although another AT2-receptor antagonist (PD 123177) was ineffective. In the present study, we examined the effects of these three compounds on the pressor and dipsogenic response to centrally-injected AII in conscious, male Long Evans rats, and the effect of EXP 3174 and PD 123319 on drinking in response to water-deprivation in Brattleboro rats. In Long Evans rats, AII-induced water intake and pressor effects were inhibited by EXP 3174 and PD 123319 (although with different time courses). In contrast, PD 123177 had little effect on the pressor response to i.c.v. AII, but enhanced its dipsogenic action. Following 8 h water deprivation in Brattleboro rats, neither EXP 3174 nor PD 123319 inhibited drinking when water was returned. These data indicate that EXP 3174 and PD 123319 inhibit thirst evoked by centrally injected AII, but not that caused by extracellular dehydration. In addition, since the putative AT2-receptor antagonists PD 123319 and PD 123177 have the opposite effects on i.c.v. AII-induced water intake, these results cannot be easily reconciled with a simple model of thirst in which AT2-receptors are involved in a final common pathway for drinking.
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PMID:Effects of angiotensin II AT1- or AT2-receptor antagonists on drinking evoked by angiotensin II or water deprivation in rats. 792 26

There is increasing evidence that an activated intrarenal renin-angiotensin system (RAS) alters renal hemodynamics and fluid balance and that such events may lead to the development of hypertension. To examine the role of the glomerular RAS in the development of hypertension in the spontaneously hypertensive (SHR) rat, we studied angiotensin (ANG) II receptors in isolated glomeruli from young (4- to 5-wk-old) and adult (10- to 12-wk-old) SHR and from age-matched, normotensive Wistar-Kyoto (WKY) rats. Glomerular ANG II receptor density in young SHR is 3-fold higher than in age-matched WKY rats (2033 +/- 154 versus 742 +/- 151 receptors/microns2; p < 0.05) and 1.5-fold higher than in adult SHR and WKY rats (1128 +/- 85 and 1198 +/- 181 receptors/microns2, respectively; p < 0.05). Additional studies demonstrated that the differences in receptor density are not related to disparity in receptor occupancy and that they are also independent of systemic ANG levels. Suppression of RAS by ANG converting enzyme inhibitors resulted in a 3-fold increase in receptor density in young SHR rats and a 4.5-fold increase in young WKY rats; receptor density remained greater in young SHR rats (5915 +/- 318 versus 3358 +/- 234 receptors/microns2, p < 0.05). Furthermore, competitive binding experiments using the nonpeptide ANG II antagonists losartan (AT1) and PD 123319 (AT2) indicate that the greater ANG II receptor density in the young SHR rats represents an increase in the number of a single population of AT1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glomerular losartan (DuP 753)-sensitive angiotensin II receptor density is increased in young spontaneously hypertensive rats. 793 16

1. This study was undertaken in cultured vascular smooth muscle cells to characterize the angiotensin II (AII) AT1 receptor subtype involved in DNA synthesis because (i) the AII receptor involved in vascular proliferation has previously been characterized in vitro in rat aortic cells and identified as an AT1 subtype and (ii) molecular cloning and biochemical studies have provided evidence for the existence of different AT1 receptor subtypes. 2. In cultured rat aortic vascular smooth muscle (VSMC), exposure to AII (0.1 to 100 nM) resulted in a concentration-dependent increase in [3H]-thymidine incorporation with an EC50 of 1.41 +/- 0.51 nM. Maximal stimulation was observed in the presence of 100 nM AII and corresponded to 271 +/- 40% of basal [3H]-thymidine incorporation. 3. To characterize the AII AT1 receptor subtype involved in this effect, cells were exposed to AII (3 nM) in the absence or presence of increasing concentrations of various AII receptor antagonists. The stimulatory effect of AII (3 nM) on [3H]-thymidine incorporation in VSMC was antagonized by the non-selective AT1/AT2 receptor antagonist, [Sar1, Ile8]-AII (IC50 = 5.6 nM), by the AT1A/AT1B receptor antagonist, losartan (IC50 = 10.5 nM) and the AT1 receptor antagonist, L-158809 (IC50 = 0.20 nM). The selective AT2 receptor ligand, CGP 42112A, antagonized AII-induced [3H]-thymidine incorporation with an IC50 of 6.3 +/- 1.3 microM while the AT2/AT1B receptor antagonist, PD 123319, was found to be almost inactive (IC50 > 10 microM). 4. Under the same experimental conditions, angiotensin III (AIII) was found to be at least 50 times less potent than All with an apparent EC50 of 81.6 +/- 7.7 nM. At the highest concentration tested (10 microM),the effect of AIII corresponded to 327 +/- 61% of basal [3H]-thymidine incorporation.5. These results confirm that All can stimulate DNA synthesis in VSMC through an AT, receptor.Furthermore, the pharmacological characterization of this AT1 receptor is compatible with the ATlA receptor subtype recently described on cultured mesangial cells since (i) the ATIA/ATIB receptor antagonist losartan is active at nanomolar concentrations, (ii) micromolar concentrations of the AT2/AT1B receptor antagonist PD 123319 are ineffective at antagonizing the AII-induced [3H]-thymidine incorporation and (iii) All is at least 50 times more potent than AIII in stimulating DNA synthesis.
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PMID:Characterization of the angiotensin II AT1 receptor subtype involved in DNA synthesis in cultured vascular smooth muscle cells. 795 81

The purpose of this study was to investigate whether the selective angiotensin AT2 receptor ligands, CGP 42112B (Nic-Tyr-(N alpha-benzoyloxycarbonyl-Arg)Lys-His-Pro-Ile-OH) and PD 123319 ((s)-1-[[4-(dimethylamino)-3-methyl-phenyl]methyl]-5-(diphenylacetyl+ ++)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]-pyridine-6-carboxylic acid) are agonists at angiotensin receptors influencing blood pressure and renal function in the enalaprilat-treated anesthetized rat. The agonist angiotensin II significantly increased blood pressure and renal vascular resistance. Glomerular filtration rate was unchanged by angiotensin II. Effective renal blood flow decreased significantly in response to angiotensin II leading to a significant increase in filtration fraction. Angiotensin II did not induce significant change in urinary potassium excretion or free water formation but significantly increased both urine volume and urinary sodium excretion. At doses up to 3 orders of magnitude greater than angiotensin II, CGP 42112B also significantly increased blood pressure, filtration fraction, glomerular filtration rate, urine volume and urinary sodium excretion, but did not significantly affect effective renal blood flow or renal vascular resistance. The selective angiotensin AT2 receptor ligand PD 123319 had no significant effects on blood pressure nor any measured parameter of renal function. The changes in blood pressure and renal function produced by angiotensin II and CGP 42112B could be completely blocked by the angiotensin AT1 receptor antagonist losartan. The results therefore only support a role for angiotensin AT1 receptors and not angiotensin AT2 receptors in the control of renal function in the rat and demonstrate that at high doses the angiotensin AT2 selective ligand CGP 42112B behaves as an agonist at angiotensin AT1 receptors.
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PMID:Renal actions of the angiotensin AT2 receptor ligands CGP 42112 and PD 123319 after blockade of the renin-angiotensin system. 795 90

The effects of the angiotensin II (ANG II) AT2 ligand PD 123319 and the AT1 antagonist losartan on cerebral blood flow (CBF) were studied during hemorrhagic hypotension in anesthetized rats using laser-Doppler flowmetry. In the control group CBF remained stable when mean arterial blood pressure (MABP) was lowered from 84 mmHg (baseline) to 45 mmHg, whereafter there was a pressure dependent decrease in CBF indicating inadequacy of autoregulation. Cerebrovascular resistance (CVR) was reduced until MABP 40 mmHg, where a maximum dilation was reached. PD 123319 dose-dependently (3-30 mg/kg i.v.) increased CVR through all blood pressures. Losartan 3 mg/kg i.v. had an effect similar to PD 123319. Selective stimulation of AT2 receptors with intravenous ANG II infusion, in the presence of AT1 receptor blockade by losartan, also increased CVR. As a result, reduced CBF was seen in the treatment groups. The effects of ANG II and PD 123319 30 mg/kg were antagonized by the nonselective ANG II antagonist Sar1,Ile8-ANG II (4 micrograms/kg/min i.v.). None of the treatments affected baseline CBF. The results confirm that ANG II contributes to cerebrovascular resistance and participates in the regulation of CBF apparently through AT2 receptors.
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PMID:Angiotensin II AT2 receptor stimulation increases cerebrovascular resistance during hemorrhagic hypotension in rats. 797 28

The effects of angiotensin II on the vasopressor responses to the selective alpha 1-adrenoceptor agonist, phenylephrine, in intact and sympathectomized rats were investigated. Infusion of angiotensin II at subpressor doses significantly enhanced the pressor effects of phenylephrine in intact rats. We also found that in the chemically sympathectomized rat, where prejunctional sympathetic function is impaired, the effects of angiotensin II infusion on the pressor effects of phenylephrine were similar to those obtained in intact rats. Furthermore, pretreatment with valsartan ((S)-N-valeryl-N-([2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl)-val ine), a new selective angiotensin AT1 receptor antagonist, antagonized the effects of angiotensin II on phenylephrine-mediated pressor responses, whereas the administration of the selective angiotensin AT2 receptor antagonist, PD 123319 (1-[[4-(dimethylamino)-3-methylphenyl]-methyl]-5-(diphenylacetyl)- 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]-pyridine-6-carboxylic acid, ditriflouroacetate, monohydrate), injected in bolus doses of 100 micrograms/kg, did not antagonize the enhancing effect of angiotensin II. Collectively, these data suggest that angiotensin II modulates the response to phenylephrine primarily at a postjunctional level through the activation of angiotensin AT1 receptors and that the suggested prejunctional facilitation mediated by angiotensin receptors is quantitatively much less important in the intact animal.
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PMID:Postjunctional regulation by angiotensin II of alpha 1-adrenoceptor-mediated pressor responses in the rat. 800 34

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