Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The octapeptide hormone, angiotensin II, binds to two major subtypes of cell surface receptors: the AT1 and the AT2 angiotensin receptors. The important physiological and pathophysiological effects of angiotensin II on cardiovascular regulation and salt-water balance are mediated by the AT1 receptor subtype. As a consequence of the outstanding clinical success of angiotensin-converting enzyme inhibitors, the appearance of AT1 receptor inhibitors in the therapy of hypertension and other cardiovascular diseases was preceded with great expectations. The available experimental and clinical data indicate that the first AT1 receptor inhibitor, losartan, has the same therapeutic potential as angiotensin-converting enzyme inhibitors, but it does not evoke the angiotensin-independent side-effects of ACE inhibitors, such as dry cough or angioedema. The physiological importance and the biochemical, molecular biological and pharmacological properties of AT1 and AT2 receptors are reviewed in this paper, and a summary of the available clinical data is presented.
 ...
PMID:[AT1 angiotensin receptor inhibition as a new therapeutic possibility]. 941 27

In this report a model is developed for the formation of chromosome aberrations by approximating interphase chromosomes as random-walk Gaussian chains. The following results support the model: (1) The ratio of dicentrics to centric rings (F) was calculated for the case of equal-sized metacentric chromosomes in a spherical nucleus: F = 4-23, which agrees well with the experimental range of 5-20 reported in the literature for human lymphocytes. (2) The prediction of the model that the probabilities for intrachromosomal and interchromosomal exchanges are inversely proportional to nuclear volume agrees well with data for chromosome exchanges in lymphocytes compared to normal fibroblasts, and with data for survival of plateau-phase Chinese hamster V79 cells after postirradiation treatment with hypertonic salt solutions. (3) The prediction of the model that the probability of interchromosomal exchanges is greater in spherical nuclei than in flat nuclei agrees with experimental data for differences in survival of human fibroblasts (ataxia telangiectasia and normal) irradiated as monolayers and plated immediately or several hours (delayed plating) after irradiation.
 ...
PMID:Gaussian-chain model for the formation of chromosome aberrations. 945 98

It is well-known that cardiac hypertrophy and arterial and renal dysfunction are serious complications of hypertension. Therefore, we investigated the chronic effects of 606A (2-propyl-3-[2'(1H-tetrazole-5-yl)biphenyl-4-yl]methyl-5-acetyl-4,5,6,7- tetrahydro imidazo [4,5-c]pyridine-4-carboxylic acid disodium salt), a novel AT1-receptor antagonist, on these complications of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP) using Wistar Kyoto rats (WKY) as the control. After 8 weeks treatment from 16 weeks of age with 606A by a subcutaneously implanted osmotic pump, cardiac function, cardiac weight, acetylcholine-induced endothelium-dependent relaxation in the isolated aorta and renal function were estimated. Furthermore, wall thickness of the left ventricle was studied morphologically. We found that 606A (0.3 mg, 1 mg and 3 mg/head/day) dose-dependently lowered blood pressure without any effects on heart rate in SHRSP. Long-term treatments with 606A significantly reduced cardiac weight, left ventricular wall thickness and left ventricular end diastolic pressure, whereas it did not affect cardiac contractility. Endothelium-dependent relaxation of the aorta was recovered, and total protein excretion as well as total protein excretion/creatinine excretion ratio was reduced to the level of WKY by the treatment. These results suggest that 606A not only has a hypotensive effect but also protects cardiac, renal and vascular tissues from complications of hypertension. Thus, 606A could be an useful drug for treatment of hypertension.
 ...
PMID:A novel angiotensin II-receptor antagonist, 606A, induces regression of cardiac hypertrophy, augments endothelium-dependent relaxation and improves renal function in stroke-prone spontaneously hypertensive rats. 954 Dec 81

Both brain ouabain-like activity ("ouabain") and brain angiotensin II (ANG II) contribute to the sympathoexcitatory and pressor responses to high sodium intake in spontaneously hypertensive (SHR) and Dahl salt-sensitive (Dahl S) rats. To assess whether increases in cerebrospinal fluid (CSF) sodium can mimic this pattern of changes, Wistar rats were chronically infused with artificial CSF (aCSF) or sodium-rich aCSF (0.8 or 1.2 M sodium) intracerebroventricularly through osmotic minipumps for 14 days. Sodium-rich aCSF (0.8 M) was also infused intracerebroventricularly for 2 wk concomitantly with either antibody Fab fragments that bind ouabain and related steroids with high affinity, gamma-globulins as control (200 micrograms/day for both), or the AT1 blocker losartan (1 mg.kg-1.day-1). Sodium-rich aCSF increased CSF sodium from 146 +/- 2 to 152 +/- 2 (0.8 M) and 160 +/- 3 (1.2 M) mmol/l, and increased brain "ouabain" in the hypothalamus, pituitary, and pons. In conscious rats, sodium-rich aCSF increased baseline mean arterial pressure (MAP), enhanced MAP, heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to intracerebroventricular alpha 2-adrenoceptor agonist guanabenz and air stress, and desensitized arterial and cardiopulmonary baroreflex control of HR and RSNA. These effects were largely prevented by intracerebroventricular Fab fragments or losartan. Thus, in Wistar rats, both brain "ouabain" and the brain renin-angiotensin system contribute to sympathoexcitation, impairment of baroreflexes, and hypertension caused by chronically increased CSF sodium. The similar patterns of changes caused by CSF sodium in Wistar rats and by high sodium intake in SHR and Dahl S rats indicate that if high sodium intake increases central sodium, such changes may contribute to sympathoexcitation and hypertension.
 ...
PMID:Brain "ouabain," ANG II, and sympathoexcitation by chronic central sodium loading in rats. 957 31

ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.
 ...
PMID:Angiotensin-converting enzyme inhibitors. 957 53

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.
 ...
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.
 ...
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

This study aimed to investigate the role of endogenous angiotensin II (ANGII) in the upregulation of ANG-II AT1 receptors in adrenal glands during a low-salt intake. To this end male Sprague-Dawley rats were fed a low-salt diet (0.2 mg/g) for 10 days and were treated with the ANGII-AT1 receptor antagonist losartan (40 mg/kg per day) for 2 days, and adrenal mRNA levels for ANGII AT1A and AT1B receptors were determined by RNase protection. The low-salt diet increased AT1A and AT1B receptor mRNA levels by 90% and 220%, respectively. Losartan treatment did not change the basal AT1A mRNA level, but decreased AT1B mRNA by 50%. Treatment of rats on a low-salt diet with losartan did not change the increase of AT1A mRNA but significantly attenuated the increase of AT1B mRNA to 90% of the control value. Stimulation of endogenous ANGII levels by unilateral renal artery clipping for 2 days lowered AT1A mRNA by 25% and increased AT1B mRNA by 30%. Additional treatment with losartan did not affect the decreased AT1A mRNA levels in rats with a unilateral renal artery clip, but significantly attenuated the increase of AT1B mRNA. These findings suggest that sodium deficiency stimulates adrenal AT1A and AT1B receptor mRNA levels primarily via an ANGII-AT1-independent mechanism. The preferential increase of adrenal AT1B mRNA during a low-salt intake could be explained by the elevation of endogenous ANGII levels during sodium deficiency, suggesting that endogenous ANGII acts as an enhancer for adrenal AT1B but not for AT1A receptor gene expression via ANGII-AT1 receptors.
 ...
PMID:Positive feedback regulation of angiotensin II-AT1B receptor gene expression in rat adrenal glands. 964 12

This review describes how angiotensin AT1 receptor antagonists (eg, candesartan cilexetil, losartan) effectively protect against end-organ damage including stroke, cardiac hypertrophy, renal dysfunction, glomerulosclerosis, and/or vascular hypertrophy in the models of stroke-prone spontaneously hypertensive rats (SHRSP), SHR, DOCA/salt hypertensive rats, Dahl hypertensive rats and/or 5/6 nephrectomised rats. Particularly in SHRSP and DOCA/salt hypertensive rats, candesartan cilexetil markedly reduced the incidence of stroke and renal injury even at doses which had no effect on blood pressure (BP), suggesting that the tissue protective effects of angiotensin AT1 antagonists are not attributable simply to the normalisation of BP. In the heart, kidney and vascular tissues of SHRSP and the kidney of DOCA/salt hypertensive rats, the mRNA levels for transforming growth factor (TGF)-beta1 and extracellular matrix components (fibronectin, collagen type I, III and IV and laminin) were increased, and the increases of the gene expression were inhibited by treatment with candesartan cilexetil. In addition, there are some reports indicating that angiotensin AT1 receptor antagonists inhibit directly hypertrophy or proliferation of cultured cardiac myocytes and nonmyocytes (fibroblast), cultured mesangial cells and cultured vascular smooth muscle cells, which were stimulated by angiotensin II. These in vitro and in vivo findings suggest that local tissue AT1 receptor stimulation, being accompanied by the increased gene expression of TGF-beta1 and extracellular matrix components may partially contribute to the pathogenesis of cardiovascular end-organ damage.
 ...
PMID:Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage. 965 51

Angiotensin II mediates its effects through angiotensin receptors. The use of specific angiotensin receptor ligands and the cloning of these receptors allows their classification. So far, the AT1, AT2 and atypical angiotensin II receptors are recognised. The AT1 receptor is responsible for the classical effects of the renin-angiotensin system such as vasoconstriction, renal salt and water retention, central osmo-control and stimulation of cell growth. The function of the AT2 receptor is far from clear but this receptor appears to be important in fetal development, cell growth inhibition and differentiation processes. This review describes the angiotensin receptors and focuses on the possible functions of the AT2 receptor.
 ...
PMID:Receptors and their classification: focus on angiotensin II and the AT2 receptor. 965 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>