UMLS:C0004135 - FACTA Search

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)

It has been shown that nitric oxide (NO) may regulate angiotensin II (Ang II) receptors in vitro. To determine whether the chronic inhibition of NO synthesis upregulates cardiac Ang II receptors in a rat model, we evaluated the in vivo effect of Nomega-nitro-L-arginine methyl ester (L-NAME) on several Ang II receptors and on the expression of AT1 receptor mRNA in heart tissue. The chronic administration of L-NAME to normal rats increased the arterial blood pressure. The number of AT1 and AT2 receptors was increased, with no change in affinity, during the first week of L-NAME administration but returned to control levels after 4 weeks of treatment. The AT1 receptor mRNA was changed parallel to AT1 receptor number. Inflammatory changes (monocyte infiltration and myofibroblast formation) in perivascular areas surrounding coronary vessels and myocardial interstitial spaces were observed during the first week. The immunohistochemistry revealed that myofibroblasts expressed AT1 receptor. AT1 receptor blockade or cotreatment with L-arginine, but not cotreatment with hydralazine, prevented the L-NAME-induced increase in Ang II receptors and inflammatory changes. In conclusion, rat cardiac Ang II receptors are upregulated at an early phase of chronic inhibition of NO synthesis. This may contribute to cardiovascular inflammatory changes in an early phase and to remodeling at the later phase, which occurs after inhibition of NO synthesis.
...
PMID:Cardiac angiotensin II receptors are upregulated by long-term inhibition of nitric oxide synthesis in rats. 975 45

The hexapeptide angiotensin (ANG) IV, a metabolic product of ANG II, has been reported to play a functional role in the regulation of blood flow in extrapulmonary tissues. Here, we demonstrate that ANG IV-specific (AT4) receptors are present in porcine pulmonary arterial endothelial cells (PAECs) and that the binding of ANG IV to AT4 receptors can be blocked by its antagonist divalinal ANG IV but not by the ANG II-, AT1-, and AT2-receptor blockers [Sar1,Ile8]ANG II, losartan, and PD-123177, respectively. ANG IV significantly increased endothelial cell constitutive nitric oxide synthase (ecNOS) activity (P < 0.05) as well as cellular cGMP content (P < 0. 001). Western blot analysis revealed that ecNOS protein expression was comparable in control and ANG IV-stimulated cells. Divalinal ANG IV but not [Sar1,Ile8]ANG II, losartan, or PD-123177 inhibited the ANG II- and ANG IV-stimulated increases in ecNOS activity and cGMP content in PAECs. Incubation in the presence of N-nitro-L-arginine methyl ester (L-NAME) or methylene blue but not of indomethacin significantly diminished ANG IV-stimulated as well as basal levels of cGMP (P < 0.001). Similarly, in situ studies with precontracted porcine pulmonary arterial rings showed that ANG IV caused an endothelium-dependent relaxation that was blocked by L-NAME or methylene blue. Collectively, these results demonstrate that ANG IV binds to AT4 receptors, activates ecNOS by posttranscriptional modulation, stimulates cGMP accumulation in PAECs, and causes pulmonary arterial vasodilation, suggesting that ANG IV plays a role in the regulation of blood flow in the pulmonary circulation.
...
PMID:Angiotensin IV receptor-mediated activation of lung endothelial NOS is associated with vasorelaxation. 984 42

It has been recently shown that angiotensin II (Ang II) is not the only active peptide of the renin-angiotensin system. Several of its degradation products including Ang III (obtained by deletion of the N terminal amino acids), Ang IV (obtained by deletion of the two N terminal amino acids), and Ang II (1-7) (obtained by deletion of the C terminal amino acid), also possess biological functions. These peptides are formed via the activity of several enzymes: angiotensin--converting enzyme, aminopeptidases A and N, neutral endopeptidase and prolylendopeptidase. Ang III possesses most of the properties of Ang II and shares the same receptors AT1 and AT2. In addition this peptide is particularly important in brain physiology and plays a major role in the secretion of arginine vasopressine. Ang IV possesses its own receptors distinct from AT1 and AT2. Some of its effects (for example, stimulation of the synthesis of the type 1 inhibitor of plasminogen activator by endothelial cells) were previously attributed to Ang II. Others effects, like renal and cerebral vasodilatation, are opposed to Ang II effects. The role of Ang IV in renal physiology remains to be determined. Ang II (1-7) exhibits direct and indirect effects, the latter resulting from Ang II (1-7)-dependent formation of nitric oxide and vasodilatory prostaglandins. Ang II (1-7) potentiates the hypotensive effect of bradykinin and plays also a major role in the control of the hydroelectrolytic balance. It possesses its own receptor: AT1-7, recognizable by (sar1-thr8) Ang II or Sarthran. Finally Ang II (1-7) is converted into Ango II (1-5), by angiotensin-converting enzyme. This peptide is inactive. All of these enzymes, peptides and receptors are present in kidney. Thus the renin-angiotensin system appears to be much more complicated than thought a few years ago, setting the problem of new therapeutic tools for the treatment of hypertension and glomerulosclerosis.
...
PMID:[Active metabolites derived from angiotensin II]. 985 79

Nitric Oxide (NO) is a gas that diffuses freely through membranes of target cells to activate cGMP formation. NO is synthesised from arginine, by a family of Nitric Oxide Synthase (NOS). In the brain, NO influences synaptic plasticity, apoptosis and development. It has been recently shown that angiotensin II (Ang II) could mediate NO production by its two types of receptors, AT1 and AT2. Since we have shown that Ang II, via the AT2 receptor could induce neurite outgrowth and morphological differentiation of NG108-15 cells, the aim of the study was to investigate if NO could be one of the second messengers involved in the Ang II effect. Using the Griess colorimetric assay, we found that Ang II, by its AT2 receptor, induced nitrite formation from NO. This effect was abolished by the N-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. We also found that treatment of the cells with S-nitroso-N-acetylpenicillamine (SNAP), an exogenous source of NO, induced the same morphological differentiation. These results demonstrate that the morphological differentiation induced by the AT2 receptor is partly due to an increase in NO production.
...
PMID:Nitric oxide, a new second messenger involved in the action of angiotensin II on neuronal differentiation of NG108-15 cells. 988 14

This review examines the recent progress in the field of angiotensin receptors. Multiplicity of these receptors was demonstrated initially on the basis of pharmacologic differences and then confirmed by expression cloning. AT1 receptors are predominant in the adult. They are widely distributed and mediate all of the known biologic effects of angiotensin II (AngII) through a variety of signal transduction systems, including activation of phospholipases C and A2, inhibition of adenylate cyclase, opening of calcium channels, and activation of tyrosine kinases. AT2 receptors are predominant in the fetus, but also present in adult tissues such as the adrenals, ovaries, uterus, and brain. AngII via these receptors exerts effects often opposed to those mediated by the AT1 receptors. Signal transduction implicates protein tyrosine phosphatase stimulation. AT1 and AT2 receptor expressions are regulated differently, and regulation is also tissue-specific. AT1 and AT2 receptors have been demonstrated in endothelial cells. Activation of AT1 receptors results in production of vasodilatory agents, nitric oxide, and prostacyclin (PGI2), which counteract the direct vasoconstrictor effects of Ang II on the adjacent smooth muscle cells. AT1 receptors on mesangial cells, smooth muscle cells, and fibroblasts are involved in cell growth and fibrosis, the latter being due both to an increase in the synthesis and a decrease in the degradation of the main components of the extracellular matrix. These AT1 receptor-dependent effects are for the most part indirect and mediated by growth factors, cytokines, and other peptides, including endothelin, transforming growth factor-beta1, and platelet-derived growth factor. AngII is metabolized into active fragments by deletion of the terminal amino acids on both ends. AngIII and AngIV are formed by successive deletions of aspartic acid and arginine at the N terminus. AngII (1-7) is obtained by deletion of phenylalanine at the C terminus. AngIII shares the same receptors and exerts the same effects as AngII. AngIV and AngII (1-7) recognize the AT1 and AT2 receptors with a lesser affinity than AngII and, in addition, possess their own receptors that mediate effects often opposed to those of AngII.
...
PMID:Angiotensin II receptors. 989 38

Inhibition of nitric oxide synthase by L-arginine analogues was shown to attenuate the antihypertensive effect of angiotensin II (AngII) type-1 receptor blockade, thus suggesting that nitric oxide might partly mediate the systemic effect of these agents. In the present experiment, the effects of an acute administration of candesartan on arterial pressure, renal blood flow (transit time method), and resistance were assessed in anesthetized normotensive rats infused or not with NG-nitro-L-arginine methyl ester (L-NAME) (20 microg/kg per min for 60 min). Candesartan was given at a dose of 0.5 mg/kg intravenous bolus in normotensive rats. Candesartan reduced arterial pressure by 15+/-2% and renal vascular resistance by 31+/-2% in nonpretreated rats. Pretreatment by L-NAME did not affect the BP lowering effect of candesartan but blunted by 60 to 100% the renal response to candesartan. Concomitant administration of L-arginine restored the renal vasodilatory action of candesartan. Plasma renin concentration was reduced by L-NAME from 122+/-23 to 69+/-14 ng AngI/ml per h and not further modified by L-arginine (71+/-16 ng AngI/ml per h). Neither the systemic and renal hemodynamic responses to AngII nor its blockade by candesartan were affected by L-NAME. The loss of renal vasodilatory effect of candesartan during L-NAME infusion suggests that AT1 receptor blockade is associated with an increase in nitric oxide-dependent tone, which participates in the full expression of the renal vasodilatory action of AngII type-1 receptor blockade in anesthetized normotensive rats.
...
PMID:Nitric oxide participates in the renal vasodilatory effect of candesartan in anesthetized rats. 989 65

Nitric oxide (NO) is known to modulate the vascular effects of angiotensin II (AngII) in the kidney. To investigate the effect of AngII on NO release, a new technique was used that employs an NO-sensitive microelectrode to measure NO release from the vascular endothelium of perfused renal resistance arteries (tertiary branches of the renal artery or primary arcuate arteries) in vitro. The vessels were microdissected from isolated perfused rat kidneys, cannulated, and perfused at constant flow and pressure with Krebs-Ringer bicarbonate solution. The electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. Addition of AngII to the perfusate stimulated NO release in a dose-dependent manner; 0.1, 10, and 1000 nM AngII increased NO oxidation current by 85+/-18 pA (n=11), 148+/-22 pA (n=11), and 193+/-29 pA (n=11), respectively. These currents correspond to changes in effluent NO concentration of 3.4+/-0.5, 6.1+/-1.1, and 8.2+/-1.3 nM, respectively. The presence of 0.1 mM N(G)-nitro-L-arginine methyl ester in the perfusate significantly reduced the response to 10 nM AngII by 90.5+/-3.4% (n=5). Neither losartan (1 microM) nor candesartan (1 nM) significantly affected basal NO production, but both of these AT1-receptor blockers markedly blunted NO release in response to AngII (10 nM): 77+/-6% inhibition with losartan (n=8) and 63+/-9% with candesartan (n=8). These results demonstrate that AngII stimulates N(G)-nitro-L-arginine methyl ester-inhibitable NO release in isolated renal resistance arteries. Because the response was significantly blunted by AT1 receptor blockade, the findings suggest that endothelium-dependent modulation of AngII-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1 receptor-dependent NO release.
...
PMID:AT1 receptor inhibition blunts angiotensin II-stimulated nitric oxide release in renal arteries. 989 67

In this study, a nitric oxide (NO) sensor was used to examine the ability of angiotensin II (AngII), AngIV, and bradykinin (Bk) to stimulate NO release from porcine pulmonary artery (PPAE) and porcine aortic endothelial (PAE) cells and to explore the mechanism of the AngII-stimulated NO release. Physiologic concentrations of AngII, but not Bk, caused release of NO from PPAE cells. In contrast, Bk, but not AngII, stimulated NO release from PAE cells. AngIII-stimulated NO release from PPAE cells required extracellular L-arginine and was inhibited by L-nitro-arginine methyl ester. AT1 and AT2 receptor inhibition had no affect on AngII-mediated NO release or activation of NO synthase (NOS). AngIV, an AngII metabolite with binding sites that are pharmacologically distinct from the classic AngII receptors, stimulated considerably greater NO release and greater endothelial-type constitutive NOS activity than the same amount of AngII. The AngIV receptor antagonist, divalinal AngIV, blocked both AngII- and AngIV-mediated NO release as well as NOS activation. The results demonstrate that AngIV and the AngIV receptor are responsible, at least in part, for AngII-stimulated NO release and the associated endothelium-dependent vasorelaxation. Furthermore, these results suggest that differences exist in both AngII- and Bk-mediated NO release between PPAE and PAE cells, which may reflect important differences in response to these hormones between vascular beds.
...
PMID:Angiotensin II-stimulated nitric oxide release from porcine pulmonary endothelium is mediated by angiotensin IV. 1007 98

Angiotensin II receptor subtypes AT1 and AT2 are proteins with seven transmembrane domain (TMD) topology and share 34% homology. It was shown that His256, located in the sixth TMD of the AT1 receptor, is needed for the agonist activation by the Phe8 side chain of angiotensin II, although replacing this residue with arginine or glutamine did not significantly alter the affinity binding of the receptor. We hypothesized that the His273 located in the sixth transmembrane domain of the AT2 receptor may play a similar role in the functions of the AT2 receptor, although this residue was not identified as a conserved residue in the initial homology comparisions. Therefore, we replaced His273 of the AT2 receptor with arginine or glutamine and analyzed the ligand-binding properties of the mutant receptors using Xenopus oocytes as an expression system. Our results suggested that the AT2 receptor mutants His273Arg and His273 Glu have lost their affinity to [125I-Sar1-Ile8]Ang II, a peptidic ligand that binds both the AT1 and AT2 receptors and to 125I-CGP42112A, a peptidic ligand that binds specifically to the AT2 receptor. Thus, His273 located in the sixth TMD of the AT2 receptor seems to play an important role in determining the binding properties of this receptor. Moreover, these results along with our previous observation that the Lys215 located in the 5th TMD of the AT2 receptor is essential for its high affinity binding to [125I-Sar1-Ile8]Ang II indicate that key amino acids located in the 5th and 6th TMDs of the AT2 receptor are needed for high affinity binding of the AT2 to its ligands.
...
PMID:Role of the His273 located in the sixth transmembrane domain of the angiotensin II receptor subtype AT2 in ligand-receptor interaction. 1020 47

The potential antithrombotic action of losartan, an AT1 receptor antagonist, administered to two-kidney, one-clip rats (2K1C) in an experimental model of venous thrombosis was evaluated. The involvement of nitric oxide (NO) in this effect was also studied. Venous stasis was induced by ligation of the vena cava. Losartan after single dose (10 mg/kg, p.o.) significantly reduced the venous thrombus growth. The antithrombotic action of losartan in 2K1C rats was abolished by N(G)-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg s.c.) and restored by L-arginine (1000 mg/kg s.c.). Platelet adhesion to fibrillar collagen significantly decreased after administration of losartan. No changes in primary hemostasis and platelet aggregation were observed. Moreover, coagulation parameters such as activated partial thromboplastin time, prothrombin time and euglobulin clot lysis time were found unchanged after losartan administration either in systemic circulation or at the place of thrombus formation. Our results indicate that antithrombotic activity of losartan in 2K1C rats is NO--dependent; observed inhibition of platelet adhesion could also play a role in this phenomenon.
...
PMID:Antithrombotic activity of losartan in two kidney, one clip hypertensive rats. A study on the mechanism of action. 1021 Jan 58

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