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

An AT1-specific angiotensin II receptor antagonist (GR117289; 1 mg/kg I.V. bolus) was administered daily to ten chronically catheterized, normotensive ewes during late pregnancy (from 126 +/- 1 days) until parturition (139 +/- 1 days); five control animals received an equivalent volume of vehicle solution. Following drug administration, mean maternal blood pressure decreased from 87 +/- 1 mmHg to a minimum of 79 +/- 1 mmHg at 0.5 h (P < 0.05; n = 10) and remained low for 4-6 h without any concomitant change in fetal blood pressure or maternal and fetal heart rates. In animals fitted with flow probes, uterine blood flow decreased from 443 +/- 21 to 363 +/- 27 ml/min at 0.5 h post-drug (P < 0.05; n = 6); this change was positively correlated with the reduction in maternal blood pressure. The mean decrements in uterine and umbilical blood flows measured by steady-state infusion of tritiated water were -611 +/- 171 ml/min at 4-6 h (P < 0.05; n = 5) and -71 +/- 19 ml/min at 0.5-1 h (P < 0.05; n = 5), respectively. Significant reductions (P < 0.05; n = 10) in fetal arterial oxygen tension (-1.6 +/- 0.4 mmHg), saturation (-6.6 +/- 1.6%) and content (-0.3 +/- 0.1 mumol/ml) were evident at 0.5 h post-drug and were maintained for 6-12 h. Umbilical oxygen delivery decreased at 0.5-1 h following drug administration (P < 0.01; n = 5), but was unaccompanied by any significant change in fetal oxygen consumption. Chronic decreases in daily fetal pH and blood oxygen content occurred in GR117289-treated ewes. There were no significant differences in gestational length or neonatal outcome between vehicle- and GR117289-treated groups of ewes with single fetuses.
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PMID:Haemodynamic responses to an angiotensin II receptor antagonist (GR 117289) in maternal and fetal sheep. 778 19

The distribution of the AT1 and AT2 subtypes of angiotensin II receptor was mapped in the adult human central nervous system using quantitative in vitro autoradiography. Binding in all forebrain, midbrain, pontine, medullary and spinal cord sites where angiotensin II receptors have previously been described is of the AT1 subtype, as is binding in the small and large arteries in the adjacent meninges and in choroid plexus. By contrast, both AT1 and AT2 receptors occur in the molecular layer of the cerebellum. Angiotensin II AT1 receptors in the brain show a moderate degree of conservation across mammalian species studied so far, whereas expression of AT2 receptors is more variable, and is more restricted in the human CNS than in many other mammals. These differences between the subtype distributions in humans and other animals indicate the need for care when extrapolating the results of animal studies involving the brain angiotensin system.
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PMID:Angiotensin II receptor subtypes in the human central nervous system. 779 34

The kidney is not only the source of circulating renin, which determines the plasma concentration of angiotensin II, but it is also one of the main targets of angiotensin II. Thus, angiotensin II exerts an important physiologic influence on renal function through its ability to modulate renal hemodynamics as well as glomerular and tubular functions. Moreover, angiotensin II appears to contribute to the progressive deterioration of renal function commonly observed in renal diseases. The availability of new orally active, nonpeptide angiotensin II receptor antagonists lacking agonistic or kinin- and prostaglandin-inducing properties has offered the possibility of investigating further the renal influence of angiotensin II. Thus, it is now clear that most if not all renal effects of angiotensin II are mediated by the activation of AT1 receptors, although the AT2 subtype is present in the kidney. Furthermore, increasing experimental evidence indicates that the long-term renal protective effect of angiotensin-converting enzyme inhibitors is indeed due to the inhibition of the renin-angiotensin system rather than to the activation of non-angiotensin II mechanisms.
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PMID:Angiotensin II receptor antagonists and the kidney. 780 52

The two subtypes (AT1A and AT1B) of the type 1 (AT1) angiotensin II receptor mRNA were localized by in situ hybridization in rat fetal tissues from day 11 to 19 of gestation and in the young rat from day 0 to 10 postpartum, by use of 35S-labeled cRNA probes. Both subtype mRNAs were present in the kidney and in the adrenal gland. Organs such as liver, lung, heart, and undifferentiated mesenchymes expressed only AT1A mRNA. In contrast to the adult, only AT1A subtype was expressed during fetal and postnatal periods in the pituitary gland. Large blood vessels (e.g., aorta and cerebral arteries) expressed exclusively AT1A mRNA during fetal stages. The expression of each subtype appears to be differentially regulated, in a tissue- and age-specific way. This spatotemporal regulation of AT1A and AT1B expression suggests that angiotensin II could act as a differentiation factor during organogenesis in addition to its classical role as a regulator of the cardiovascular system.
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PMID:Ontogeny of the two angiotensin II type 1 receptor subtypes in rats. 781 Jun 23

The rapid expansion of our knowledge of angiotensin receptors has been led by the development of subtype-specific angiotensin II receptor antagonists and by the cloning and sequencing of the AT1 receptor in angiotensin II. Although some actions of angiotensin II have been attributed to AT2 subtype receptors, the importance of these binding sites remains elusive. Nonpeptide, AT1-selective antagonists, such as losartan, block virtually all of the well-known effects of angiotensin II in mammalian cells. The effects of losartan are now being confirmed by the rapidly developing class of nonpeptide, AT1-selective angiotensin II receptor antagonists. In rodents, subtypes of the AT1 receptor have been cloned and designated AT1A and AT1B, but they have not been functionally distinguished. Such isoforms have not been identified for human AT1 receptors. Importantly, it now appears that the AT2 receptor has been cloned. The angiotensin receptors undergoing intense study are those in fetal tissue, brain, endothelial cells, and fibroblasts. Angiotensin II-induced growth and cardiovascular hypertrophy are the focus of broad-based research efforts. The clinical relevance of angiotensin II receptor subtypes is unknown, but there is growing evidence that AT1-selective agents are effective inhibitors of the angiotensin system in humans.
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PMID:Human angiotensin receptor subtypes. 785 Apr 6

We examined the expression of angiotensin II receptor subtypes and angiotensin-converting enzyme in the rat aorta and carotid artery at 1, 2, 4, 8, 15, and 30 days after balloon catheter injury or sham surgery. The AT1 receptor expression was enhanced in the neointima at 8 days in the aorta and carotid artery compared to that in intact media. Maintenance of the high expression of AT1 receptors in the neonintimal tissue at 15 and 30 days was localized to a subpopulation of neointimal cell close to the lumen of the vessel and was correlated to the distribution of smooth muscle cells immunoreactive to proliferating cell nuclear antigen. During the initial stages after injury, binding of [125I]351A to angiotensin-converting enzyme was significantly decreased in both the intima/media layers as well as adventitia in carotid artery and aorta. Binding of [125I] 351A to angiotensin-converting enzyme was significantly lower in the neointima compared to that in the intima/media of intact vessels. Our results reveal that the expression of AT1 receptors is heterogeneous in the neointima, and suggest that enhanced expression of AT1 receptors in the balloon catheter-injured carotid artery and aorta may be limited to proliferating intimal smooth muscle cells.
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PMID:Heterogeneous expression of angiotensin II AT1 receptors in neointima of rat carotid artery and aorta after balloon catheter injury. 785 71

[125I]L-735,286, a new potent and AT1-selective nonpeptide angiotensin II receptor radioligand, bound saturably to whole adrenal membranes. Scatchard and Hill plot analysis indicates a single class of high affinity (Kd = 0.5 nM) binding sites. The potencies of various angiotensin II agonists and antagonists in displacing specific [125I]L-735,286 binding are in good agreement with their potencies in displacing the binding of [125I]Sar1,Ile8-AII to adrenal AT1 receptors. The AT2 selective ligand, PD121981 had no effect on specific [125I]L-735,286 binding. In autoradiographic studies using rat kidney slices, specific labeling of [125I]L-735,286 was abolished by coincubation with saralasin. Collectively, the data indicated that [125I]L-735,286 represents a new, potent nonpeptide antagonist radioligand suitable for the study of angiotensin II AT1 receptors.
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PMID:Characterization of the binding of [125I]L-735,286: a new nonpeptide angiotensin II AT1 receptor radioligand. 786 41

The effects of an angiotensin II receptor (AT1) antagonist on sympathetic nervous responses to a mental arithmetic task and a cold pressor test were investigated using a placebo-controlled, single-blind design in 8 patients with essential hypertension (53 +/- 3 years). All patients received a placebo for 2 weeks (placebo run-in period), after which the control group (P; n = 4) continued to receive the placebo, while the experimental group (TCV; n = 4) received TCV-116 at 4 mg/day for 4 weeks (treatment period). After basal measurements were carried out, an arithmetic task and a cold pressor test were conducted on the last day of each period. Blood pressure (BP), heart rate (HR) and electrocardiogram (ECG) were continuously monitored. Muscle sympathetic nerve activity (MSNA) was assessed by determining the burst rate of the mean voltage neurogram obtained from the tibial nerve. Sympathovagal balance was also assessed, by determining the area ratio of the low frequency (LF: 0.05-0.15 Hz) to high frequency bands (HF: 0.16-0.5 Hz) of a power spectral analysis of HR variability (maximum entropy method). During the placebo run-in period, there were no significant differences in basal BP, HR, LF/HF or MSNA between the two groups. During the treatment period, basal mean BP in the TCV group was significantly lower (p < 0.05) than that in the P group, but there were no significant differences in basal HR, LF/HF or MSNA between the two groups. Although the arithmetic stress significantly increased BP, HR and LF/HF in both groups, MSNA was not significantly altered in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of an angiotensin receptor antagonist, TCV-116, on sympathetic nerve activity in patients with essential hypertension. 788 94

To determine whether an angiotensin II receptor antagonist (AT antagonist) could improve the impaired coronary circulation as well as induce regression of cardiac hypertrophy in the hypertensive heart, and to elucidate whether the nitric oxide system in the coronary artery was involved in this mechanism, the AT1 antagonist, TCV-116 (10 mg/kg), was administered orally to spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY), and coronary flow was measured in the isolated hearts. High systolic blood pressure in SHR was significantly reduced by a 2-week treatment with TCV. Left ventricular (LV) hypertrophy in SHR regressed after TCV treatment, while LV weight in WKY was not reduced. Total minimum coronary vascular resistance (MCVR) obtained with adenosine (10(-5) M) infusions in a Langendorff apparatus was significantly greater in SHR than in WKY. Increased MCVR in SHR was reduced after TCV treatment. Coronary perfusion with NG-monomethyl-L-arginine monoacetate (L-NMMA) increased coronary vascular resistance (CVR) in WKY, while it failed to increase CVR in SHR. TCV treatment restored the responses to L-NMMA in SHR. These findings suggest that the AT1 antagonist, TCV-116, lowered the high blood pressure in SHR, concomitantly improving the impaired coronary circulation, and that it induced regression of the cardiac hypertrophy. The suppressed nitric oxide (NO) system in the coronary vessels in SHR appeared to be activated by TCV treatment.
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PMID:Effect of an angiotensin II receptor antagonist, TCV-116, on cardiac hypertrophy and coronary circulation in spontaneously hypertensive rats. 788 11

We tested the hypothesis that mineralocorticoids potentiate angiotensin II-stimulated phospholipase C activation through an increased number of angiotensin II receptors in cultured rat aortic vascular smooth muscle cells. Exposure of cells to aldosterone for 24 h resulted in concentration-dependent increases in angiotensin II receptor binding. Via studies of angiotensin II displacement by non-peptide receptor antagonists, both basal and upregulated angiotensin II receptors were found to be of the AT1 subtype. Incubation with 1 microM aldosterone resulted in 50-100% enhancement of angiotensin II (100 nM)-stimulated diacylglycerol formation and intracellular calcium mobilization. Exposure to 100 nM 1,25-(OH)2VitD3, which did not upregulate angiotensin II receptors, did not potentiate stimulated inositol phosphate formation. Incubation with aldosterone resulted in potentiation of inositol phosphate formation upon receptor occupation (100 nM angiotensin II) but not upon post-receptor stimulation (25 mM NaF/10 microM AlCl3). Aldosterone did not increase basal phospholipase C activity or content of the inositol trisphosphate precursor phosphatidylinositol-4,5-bisphosphate. These data are consistent with the hypothesis that aldosterone potentiates angiotensin II-stimulated, phospholipase C-dependent intracellular signals solely by coupling to an increased number of angiotensin II receptors. This mechanism may contribute to the sensitized vascular responses to angiotensin II observed in states of mineralocorticoid excess.
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PMID:Mechanisms of enhanced angiotensin II-stimulated signal transduction in vascular smooth muscle by aldosterone. 796 4


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