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

Angiotensin II (ANG II), as a single factor, induces proliferation in a cultured murine mesangial cell line (MMC). This study was undertaken to evaluate a possible influence of atrial natriuretic peptide (ANP) on this ANG II-induced proliferation. ANP (10(-7) M) for 2 min significantly increased intracellular cGMP levels in MMC. This increase in cGMP was totally abolished when cells were preincubated for 5 min with 10(-7) M ANG II. Stimulation of intracellular cGMP formation by sodium nitroprusside was also decreased in the presence of ANG II. The ANG II-mediated inhibition of ANP-stimulated intracellular cGMP levels was blocked by Dupont 753, suggesting signal transduction through ANG II receptors of the AT1 class. ANP (10(-7) M) for 24 h completely abolished the ANG II-induced proliferation in MMC. However, 10(-7) M ANP had no significant effect on mitogenesis induced by platelet-derived growth factor or epidermal growth factor. Furthermore, ANP reduced the ANG II-stimulated expression of the proliferating cell nuclear antigen, a cofactor of polymerase delta that is active in the S-phase of the cell cycle. The addition of 10(-3) M N-monobutyryl-guanosine 3':5'-cyclic monophosphate or 8-bromo-guanosine 3':5'-cyclic monophosphate also blocked the ANG II-induced proliferation. ANP (10(-7)) M for 24 h had no significant influence on the expression (number and dissociation constant) of ANG II receptors as determined by binding assays. These results suggest that, besides the previously shown vasoconstrictive and vasodilating effects, complex interactions between ANG II and ANP exist that can modulate mesangial cell growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II-induced proliferation of cultured murine mesangial cells: inhibitory role of atrial natriuretic peptide. 136 89

Ever since the identification of two distinct Ang II receptor subtypes, the function of the AT2 receptor has been a subject of debate. As opposed to the AT1 subtype, this receptor does not interact with G-proteins in most cell lines and tissues. We show here that, in intact PC12W cells which express only AT2 receptors, Ang II significantly decreases basal and atrial natriuretic peptide (ANP)-stimulated cGMP concentration. This effect is mimicked by the AT2 selective agonist CGP 42112, and is not prevented by the AT1 selective antagonist losartan, indicating that this is an AT2 receptor mediated response. The lack of effect of the phosphodiesterase (PDE) inhibitor IBMX shows that this mechanism does not involve PDE stimulation. This is confirmed by the finding that neither Ang II or CGP 42112 affect the Ca++/calmodulin dependent cGMP PDE activity. Furthermore Ang II and CGP 42112 have no effect on nitroprusside-stimulated cGMP levels in these cells, thus ruling out interactions between the AT2 receptor and soluble guanylate cyclase. These data indicate that the AT2 receptor mediated decrease of cGMP is due to the selective inhibition of particulate guanylate cyclase (pGC) activity. In an accompanying paper we report that interaction of Ang II with the AT2 receptor in the same cells results in the stimulation of phosphotyrosine phosphatase (PTPase) activity. Interestingly, the PTPase inhibitors sodium orthovanadate and phenylarsine oxyde, but not the Ser/Thr phosphatase inhibitor okadiac acid, inhibitthe Ang II and CGP 42112 induced decreases in cellular cGMP concentration. These findings suggest that stimulation of PTPase activity may be involved in the regulation of pGC activity via AT2 receptors.
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PMID:Angiotensin AT2 receptor mediated inhibition of particulate guanylate cyclase: a link with protein tyrosine phosphatase stimulation? 752 2

Astroglial cells derived from the mammalian central nervous system contain a wide variety of peptide receptors, including specific sites for angiotensin II (AII) and atrial natriuretic peptide (ANP). The AII receptors present in these cells are primarily of the AT1 subtype. The ANP receptors present in these cells consist of a mix of ANP-A and ANP-B sites ("biological receptors") and also ANP-C sites ("clearance receptors"). Available evidence indicates that activation of AII receptors results in a stimulation of astroglial proliferation, whereas ANP has an antiproliferative effect in these cells. Intracellular pathways which may mediate these effects of AII and ANP on cell proliferation are discussed, including the presentation of novel data on the activation of protein kinase C and of glucose uptake by AII. We also consider the possibility that the opposing actions of AII and ANP on astroglial proliferation may represent another facet of the mutual antagonism between these two peptides, which has been observed throughout mammalian systems.
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PMID:Peptide receptors in astroglia: focus on angiotensin II and atrial natriuretic peptide. 792 41

Despite some recent reports describing the effects of AT2 receptor selective ligands in vitro and in vivo, the physiological function of this receptor is still a matter of debate. This problem stems amongst others from the difficulty in interpreting results from in vivo experiments with drugs of which it is not known whether they act as agonists or antagonists. We reported earlier that angiotensin II inhibits basal and atrial natriuretic peptide stimulated particulate guanylate cyclase activity through AT2 receptors in PC12W cells. We have used this parameter in intact PC12W cells in order to determine the pharmacological properties of different widely used angiotensin receptor ligands. We found CGP 42112 to behave as a full agonist in this system, whereas PD 123319 and Sar Ile angiotensin II act as antagonists. As expected, the AT1 antagonist losartan did not affect this response.
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PMID:Agonistic and antagonistic properties of angiotensin analogs at the AT2 receptor in PC12W cells. 838 91

We have examined the cAMP-independent regulation of cytosolic calcium concentration in rat Sertoli cells using the effect of vasoactive hormones, known as testicular paracrine regulators operating via the non-cAMP pathway, on cytosolic calcium. Calcium concentrations were estimated with dual excitation fluorimetry, using freshly isolated, fura-2/AM-loaded cells. No increase in the cellular cAMP concentration was detected after stimulation with angiotensin II (AII), vasopressin, PGF2 alpha, or atrial natriuretic peptide. Whereas both AII and vasopressin evoked a rise in cytosolic calcium from a basal level of 81.4 +/- 4 to 142.5 +/- 18 and 154.4 +/- 11 nM, respectively, PGF2 alpha had only a minimal effect (98 +/- 5 nM), and atrial natriuretic peptide no effect (86.6 +/- 9 nM). The effect of AII on calcium was blocked by the the selective AT2, but not by the AT1, receptor antagonist, indicating the selective presence on Sertoli cells of AT2 AII receptor. Similarly, the vasopressin-induced calcium response was blocked by vasopressin V1, but not by V2 receptor antagonist, consistent with the presence of V1 receptor subtype in these cells. Removal of extracellular calcium or blockade of calcium channels did not inhibit the calcium increase due to AII and vasopressin, suggesting the involvement of intracellular calcium. Thapsigargin increased the basal cytosolic calcium concentration to 137 +/- 10 nM. Depletion of intracellular calcium stores with thapsigargin before stimulation with AII or vasopressin abolished both the AII-mediated and the vasopressin-mediated calcium rise in the presence as well as the absence of extracellular calcium, indicating that the increase in calcium is predominantly derived from the thapsigargin-sensitive endoplasmic reticulum. This study indicates that calcium homeostasis of Sertoli cells might also be regulated by cAMP-independent metabolism apart from the well known cAMP-dependent pathway. Furthermore, our findings support the idea that angiotensin and vasopressin might be important paracrine regulators of Sertoli cells functions.
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PMID:Cyclic adenosine 3',5'-monophosphate-independent regulation of cytosolic calcium in Sertoli cells. 864 Dec 16

1. The chronotropic effects of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) were investigated using injections (50 micrograms in 1 ml of Tyrode solution as bolus over 1 min) directly into the sinus node artery of 21 anaesthetized and vagotomized dogs which had been pretreated with a beta-adrenoceptor antagonist. The injections were also repeated following: (a) alpha-adrenoceptor antagonism (prazosin) and muscarinic receptor antagonism (atropine); (b) inhibition of prostaglandin synthesis (indomethacin); (c) angiotensin II AT1 receptor antagonism (losartan); (d) histamine H1 (mepyramine) and H2 (cimetidine) receptor antagonism. 2. The results obtained indicate that ANP had no significant effect on the basal sinus rate, whereas CNP produced a slight but significant increase of 12 +/- 2 beats min-1. The effect of CNP was long-lasting (return to pre-injection levels after maximum effect in 17 +/- 3 min) and was not influenced by the various antagonists mentioned above. 3. During in vitro experiments on spontaneously beating right atria isolated from 6 dogs, the injection of CNP (50 micrograms in 1 ml of Tyrode solution) into the sinus node artery produced an increase in atrial rate of 14 +/- 1 beats min-1. 4. The results of this work indicate that CNP exerts a significant and prolonged positive chronotropic effect both in vivo and in vitro. Other studies are required to elucidate the mechanism of action of CNP on the heart conduction system, to ascertain the presence of natriuretic peptide receptor B in the region of the sinoatrial node and to determine the role of CNP in the control of heart rate.
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PMID:Direct chronotropic effects of atrial and C-type natriuretic peptides in anaesthetized dogs. 884 45

Phase I human studies can be used to differentiate a novel agent from existing drugs that influence the same pathway (eg, angiotensin-converting enzyme [ACE] inhibitors). Human forearm vasculature provides a useful experimental model for such studies because antagonism of local effects of agonists on resistance vasculature can be quantified, unconfounded by reflex cardiovascular responses to systemically applied agonists. In this model, inhibition of ACE with enalapril (given orally) or its active metabolite enalaprilat (given into the brachial artery) influences responses to some, but not all, vasoactive peptides that are substrates of ACE in vitro. Vasoconstrictor responses to angiotensin I (A I) are antagonized, while vasodilator responses to bradykinin are potentiated. Responses to vasoactive intestinal peptide (VIP), substance P (SP), and atrial natriuretic peptide (ANP) are unaltered by ACE inhibition. Vasodilator responses to bradykinin are antagonized by the B2-receptor icatibant and are blunted (but not abolished) by inhibition of the L-arginine/NO pathway with L-NG-monomethyl arginine. In contrast to inhibition of ACE with enalapril, blockade of the AT1 receptor with losartan results in similar inhibition of vasoconstrictor responses to both A I and angiotensin II but has no significant effect on the vasodilator action of bradykinin. The implication is that losartan provides more specific blockade of the renin-angiotensin pathway than does inhibition of ACE. The in vivo methods described in the study confirm the mechanistically relevant differentiation between AT1-receptor antagonism and ACE inhibition in humans.
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PMID:Angiotensin II-receptor (AT1) blockade in the human forearm. 891 43

Bicarbonate reabsorption was evaluated by stationary microperfusion "in vivo" early distal (ED) and late distal (LD) segments of at kidney. Intratubular pH was recorded by double-barreled of H+ exchange resin/reference (1 M KCl) microelectrodes for the determination of HCO3- reabsorption. In the presence of angiotensin II (ANG II) (10(-12) M), a significant increase in HCO3- reabsorption was observed both in ED (from 0.930 +/- 0.060 to 2.64 +/- 0.210 nmol.cm-2.s-1 in luminally perfused tubules and from 0.850 +/- 0.040 to 2.03 +/- 0.210 nmol.cm-2.s-1 during capillary perfusion) and LD segments from 0.310 +/- 0.130 to 2.16 +/- 0.151 nmol.cm-2.s-1 during luminal perfusion and from 0.530 +/- 0.031 to 2.16 +/- 0.211 nmol.cm-2.s-1 with capillary perfusion). The addition of the AT1-receptor antagonist losartan (10(-6) M) to luminal perfusion blocked luminal ANG II-mediated stimulation in ED and LD segments. 5-(N,N-hexamethylene)amiloride (10(-4) M) added to luminal perfusion inhibited luminal ANG II-mediated stimulation in ED (by 81%) and LD (by 54%) segments. The addition of bafilomycin A1 (2 x 10(-7) M) to luminal perfusion does not affect luminal ANG II-mediated stimulation in ED segments but reduces it in LD segments (by 33%). During the addition of atrial natriuretic peptide (ANP) (10(-6) M) or ANG II plus ANP in both segments, no significant differences in HCO3- reabsorption were observed. Our results indicate that luminal ANG II acts to stimulate Na+/H+ exchange in ED and LD segments via activation of AT1 receptors, as well as the vacuolar H(+)-adenosinetriphosphatase in LD segments. ANP does not affect HCO3- reabsorption in either ED or LD segments and does not impair the stimulation caused by ANG II.
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PMID:Effect of luminal angiotensin II and ANP on early and late cortical distal tubule HCO3- reabsorption. 894 91

Volume expansion has been shown to increase plasma atrial natriuretic peptide (ANP) levels, but the precise role of paracrine and autocrine factors in stretch-induced cardiac hormone release is not clear. In the present study, we report the effects of endothelin (ET) and angiotensin receptor (AT receptor) antagonists on baseline and atrial stretch-induced immunoreactive ANP (IR-ANP) and immunoreactive N-terminal ANP (IR-NT-ANP) release in vivo by using BQ-123 (ETA receptor antagonist), bosentan (ETA and ETB receptor antagonist), and losartan (AT1 receptor antagonist). Intravenous administration of BQ-123 had no significant effect on baseline hemodynamics in conscious rats, whereas bosentan (10 mg/kg) and losartan (10 mg/kg) decreased slightly (4 to 7 mm Hg, P < .05 to .001) the mean arterial pressure. Both the ETA receptor antagonist BQ-123 and ETA/ETB receptor antagonist bosentan decreased plasma ANP and NT-ANP responses to volume load (P < .05 to .001), whereas the AT1 receptor antagonist losartan had no significant effect on this response. The relative increase in plasma IR-ANP corresponding to a 3 mm Hg increase in right atrial pressure was 2.7-fold in the vehicle-treated group. BQ-123 (0.3 and 1.0 mg/kg) decreased this response 2.5- and 2.1-fold (P < .05); bosentan (3 and 10 mg/kg), 1.7-fold (P < .001) and 1.9-fold (P < .05); and bosentan (10 mg/kg)+losartan (10 mg/kg), 1.6-fold (P < .001). The responses in plasma IR-NT-ANP decreased simultaneously. These results indicate that combined inhibition of ETA/B and AT1 receptors almost completely blocks ANP response to acute volume load. Therefore, our study shows that endogenous paracrine and/or autocrine factors liberated in response to atrial wall stretch rather than myocyte stretch itself are responsible for the activation of ANP peptide secretion in response to acute volume load. Our results also show that ETA receptors are more important in the regulation of mechanical stretch-induced changes in cardiac hormone secretion than AT1 receptors.
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PMID:Combined inhibition of endothelin and angiotensin II receptors blocks volume load-induced cardiac hormone release. 897 30

The effect of angiotensin II (Ang II) on inositol phosphate (IP) production and atrial natriuretic peptide (ANP) release was studied in sliced rat atrial tissue. The ability of Ang II (10(-7) M) to stimulate IP accumulation was detected after 1 min of incubation, and the maximal increase was observed at 5 min. In (2-3H) inositol-labeled atrial tissue, Ang II induced the formation of (2-3H) inositol monophosphate (IP1) in a dose-dependent manner. The effect of Ang II (10(-7) M) on IP1 was prevented by losartan (10(-7) M) but was not affected by PD123319 (10(-7) M). Similar effects were observed on Ang II-induced ANP release in the presence of these antagonists. The mechanism of ANP liberation induced by this peptide was independent of cyclic adenosine monophosphate (cAMP) and regulated by nitric oxide (NO). The role of Ca2+ in the effect of Ang II was tested by 1,2-bis (o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM; 10(-5) M), a chelator of intracellular Ca2+ that prevented the release of ANP by Ang II stimulation. We concluded that Ang II induced IP production and ANP release through AT1 receptors. Stimulation of ANP release by Ang II was dependent on intracellular Ca2+.
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PMID:Angiotensin II-induced phosphoinositide production and atrial natriuretic peptide release in rat atrial tissue. 921 2


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