scholarly journals Angiotensin II stimulates cyclic ADP-ribose formation in neonatal rat cardiac myocytes

2000 ◽  
Vol 352 (1) ◽  
pp. 197-202 ◽  
Author(s):  
Haruhiro HIGASHIDA ◽  
Jia-Sheng ZHANG ◽  
Minako HASHII ◽  
Miyuki SHINTAKU ◽  
Chiharu HIGASHIDA ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ventricular Myocytes ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Cyclase Activity ◽  
Ventricular Muscle ◽  
Ang Ii ◽  
Adult Rats ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose

To examine the role of cyclic ADP-ribose (cADP-ribose) as a second messenger downstream of angiotensin II (Ang II) receptor activation in the heart, ADP-ribosyl cyclase activity was measured in a crude membrane fraction of ventricular myocytes. Ang II at 10–100nM increased ADP-ribosyl cyclase activity by 40–90% in the ventricular muscle of neonatal (2–4-day-old) rats, but not in fetal or adult hearts. This increase was inhibited by the Ang II antipeptide. Stimulation of ADP-ribosyl cyclase was reproduced by GTP and guanosine 5´-[γ-thio]triphosphate, and prevented by guanosine 5´-[β-thio]diphosphate. Prior treatment of the rats with cholera toxin A and B subunits also blocked the Ang II-induced activation. The density of Ang II receptors detected as [3H]Ang II binding was higher in neonatal than adult rats. These results demonstrate the existence of a signalling pathway from Ang II receptors to membrane-bound ADP-ribosyl cyclase in the ventricular muscle cell and suggest that the Ang II-induced increase in cADP-ribose synthesis is involved in the regulation of cardiac function and development.

scholarly journals Suppressor of Cytokine Signaling 3 Is Induced by Angiotensin II in Heart and Isolated Cardiomyocytes, and Participates in Desensitization

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4586-4596 ◽  
Author(s):  
Vivian C. Calegari ◽  
Rosangela M. N. Bezerra ◽  
Márcio A. Torsoni ◽  
Adriana S. Torsoni ◽  
Kleber G. Franchini ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Rat Heart ◽  
Ventricular Myocytes ◽  
Janus Kinase ◽  
Neonatal Rat ◽  
Cytokine Signaling ◽  
Ang Ii ◽  
Suppressor Of Cytokine Signaling ◽  
Rat Ventricular Myocytes ◽  
Neonatal Rat Ventricular Myocytes

Angiotensin II (Ang II) exerts a potent growth stimulus on the heart and vascular wall. Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) intracellular signaling pathway by Ang II mediates at least some of the mitogenic responses to this hormone. In other signaling systems that use the JAK/STAT pathway, proteins of the suppressor of cytokine signaling (SOCS) family participate in signal regulation. In the present study it is demonstrated that SOCS3 is constitutively expressed at a low level in rat heart and neonatal rat ventricular myocytes. Ang II at a physiological concentration enhances the expression of SOCS3 mRNA and protein, mainly via AT1 receptors. After induction, SOCS3 associates with JAK2 and impairs further activation of the JAK2/STAT1 pathway. Pretreatment of rats with a specific phosphorthioate antisense oligonucleotide to SOCS3, reverses the desensitization to angiotensin signaling, as detected by a fall in c-Jun expression after repetitive infusions of the hormone. Thus, SOCS3 is induced by Ang II in rat heart and neonatal rat ventricular myocytes and participates in the modulation of the signal generated by this hormone.

Cysteinyl leukotriene-dependent [Ca2+]iresponses to angiotensin II in cardiomyocytes

2003 ◽  
Vol 284 (4) ◽  
pp. H1269-H1276 ◽  
Author(s):  
Pinggang Liu ◽  
Derek A. Misurski ◽  
Venkat Gopalakrishnan
Keyword(s):  
Angiotensin Ii ◽  
Single Cells ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Ang Ii ◽  
Rat Cardiomyocytes ◽  
Endothelin 1 ◽  
Neonatal Rat Cardiomyocytes ◽  
Cysteinyl Leukotriene

With the use of fura 2 measurements in multiple and single cells, we examined whether cysteinyl leukotrienes (CysLT) mediate angiotensin II (ANG II)-evoked increases in cytosolic free Ca2+ concentration ([Ca2+]i) in neonatal rat cardiomyocytes. ANG II-evoked CysLT release peaked at 1 min. The angiotensin type 1 (AT1) antagonist losartan, but not the AT2antagonist PD-123319, attenuated the elevations in [Ca2+]i and CysLT levels evoked by ANG II. Vasopressin and endothelin-1 increased [Ca2+]i but not CysLT levels. The 5-lipoxygenase (5-LO) inhibitor AA-861 and the CysLT1-selective antagonist MK-571 reduced the maximal [Ca2+]i responses to ANG II but not to vasopressin and endothelin-1. While MK-571 reduced the responses to leukotriene D4 (LTD4), the dual CysLT antagonist BAY-u9773 completely blocked the [Ca2+]i elevation to both LTD4and LTC4. These data confirm that ANG II-evoked increases, but not vasopressin- and endothelin-1-evoked increases, in [Ca2+]i involve generation of the 5-lipoxygenase metabolite CysLT. The inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] antagonist 2-aminoethoxydiphenyl borate attenuated the [Ca2+]i responses to ANG II and LTD4. Thus AT1 receptor activation by ANG II is linked to CysLT-mediated Ca2+ release from Ins(1,4,5)P3-sensitive intracellular stores to augment direct ANG II-evoked Ca2+ mobilization in rat cardiomyocytes.

Effect of angiotensin II on cytosolic free calcium in neonatal rat cardiomyocytes

1991 ◽  
Vol 261 (1) ◽  
pp. C77-C85 ◽  
Author(s):  
D. C. Kem ◽  
E. I. Johnson ◽  
A. M. Capponi ◽  
D. Chardonnens ◽  
U. Lang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Acute Effect ◽  
Neonatal Rat ◽  
Free Calcium ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Rat Cardiomyocytes ◽  
Neonatal Rat Ventricular Myocytes

The effect of angiotensin II (ANG II) on cytosolic free Ca2+ concentration ([Ca2+]i) was studied in cultured neonatal rat ventricular myocytes. [Ca2+]i was estimated in groups of one to three cells by dual-wavelength microfluorometry or in cell populations using conventional fluorometry. ANG II (10(-8) M) produced an acute short-lived increase over the control basal diastolic [Ca2+]i and increased the frequency of the [Ca2+]i transients. The amplitude of the [Ca2+]i transients was decreased to 64.4% of basal values. The effect of ANG II on [Ca2+]i was blocked by the selective AT1 receptor subtype antagonist Du Pont 753 but not by the AT2 antagonist PD 123319. Removal of extracellular Ca2+ or blockade of voltage-gated Ca2+ channels in cells cultured for 5-7 days abolished the [Ca2+]i transients, but only partially diminished the effect of ANG II on [Ca2+]i. Thapsigargin, an inhibitor of sarcoplasmic reticulum Ca(2+)-Mg(2+)-ATPase, reduced or abolished the [Ca2+]i response to ANG II. Phorbol 12-myristate 13-acetate (PMA), 10(-6) and 10(-7) M, also decreased the amplitude of the Ca2+ transients similar to ANG II. Pretreatment with 10(-6) M PMA or 10(-6) M 1-oleoyl-2-acetyl-glycerol (OAG) inhibited the initial rise in [Ca2+]i and the Ca2+ transients. Thus ANG II produces an acute rise in [Ca2+]i which is derived predominantly from sarcoplasmic reticulum intracellular stores. This acute effect is followed by a significant reduction in the amplitude for the Ca2+ transient and may be mediated by activation of protein kinase C.

scholarly journals Extracellular and Intracellular Angiotensin II Regulate the Automaticity of Developing Cardiomyocytes via Different Signaling Pathways

2021 ◽  
Vol 8 ◽  
Author(s):  
Zenghua Qi ◽  
Tao Wang ◽  
Xiangmao Chen ◽  
Chun Kit Wong ◽  
Qianqian Ding ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
High Performance ◽  
Calcium Release ◽  
Ventricular Myocytes ◽  
Surface Membrane ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Underlying Mechanism ◽  
Neonatal Rat ◽  
Ang Ii

Angiotensin II (Ang II) plays an important role in regulating various physiological processes. However, little is known about the existence of intracellular Ang II (iAng II), whether iAng II would regulate the automaticity of early differentiating cardiomyocytes, and the underlying mechanism involved. Here, iAng II was detected by immunocytochemistry and ultra-high performance liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry in mouse embryonic stem cell–derived cardiomyocytes (mESC-CMs) and neonatal rat ventricular myocytes. Expression of AT1R-YFP in mESC-CMs revealed that Ang II type 1 receptors were located on the surface membrane, while immunostaining of Ang II type 2 receptors (AT2R) revealed that AT2R were predominately located on the nucleus and the sarcoplasmic reticulum. While extracellular Ang II increased spontaneous action potentials (APs), dual patch clamping revealed that intracellular delivery of Ang II or AT2R activator C21 decreased spontaneous APs. Interestingly, iAng II was found to decrease the caffeine-induced increase in spontaneous APs and caffeine-induced calcium release, suggesting that iAng II decreased spontaneous APs via the AT2R- and ryanodine receptor–mediated pathways. This is the first study that provides evidence of the presence and function of iAng II in regulating the automaticity behavior of ESC-CMs and may therefore shed light on the role of iAng II in fate determination.

Lipid signal transduction pathways in angiotensin II type 1 receptor-transfected fibroblasts

1995 ◽  
Vol 269 (2) ◽  
pp. C435-C442 ◽  
Author(s):  
Y. Wen ◽  
M. C. Cabot ◽  
E. Clauser ◽  
S. L. Bursten ◽  
J. L. Nadler
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Chinese Hamster ◽  
Receptor Activation ◽  
Signal Transduction Pathways ◽  
Ang Ii ◽  
Vascular Type ◽  
Lipid Signal ◽  
Fibroblast Line

A stable Chinese hamster ovary fibroblast line expressing the rat vascular type 1a angiotensin II (ANG II) receptor was used to study the lipid-derived signal transduction pathways elicited by type 1a ANG II receptor activation. ANG II caused a biphasic and dose-dependent increase in diacylglycerol (DAG) accumulation with an initial peak at 15 s (181 +/- 11% of control, P < 0.02) and a second sustained peak at 5-10 min (214 +/- 10% of control, P < 0.02). The late DAG peak was derived from phosphatidylcholine (PC), and the formation was blocked by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. ANG II also increased phosphatidic acid (PA) production nearly fourfold by 7.5 min. In the presence of ethanol, ANG II markedly increased phosphatidylethanol (PEt) formation, indicating activation of phospholipase D (PLD). ANG II was shown to increase the mass of three separate PA species, one of which apparently originated from DAG kinase action on PC-phospholipase C (PLC)-produced DAG, providing evidence for PC-PLC activity. ANG II also formed a third PA species, which originated neither from PLD nor from DAG kinase. These results demonstrate that multiple lipid signals propagated via collateral stimulation of PLC and PLD are generated by specific activation of the vascular type 1a ANG II receptor.

Abstract 476: Renal AT2 Receptor Activation Prevents Sodium Retention And Lowers Blood Pressure In Angiotensin II-Dependent Hypertension

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Shetal H Padia ◽  
Nancy L Howell ◽  
Brandon A Kemp ◽  
John J Gildea ◽  
Susanna R Keller ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Activation ◽  
Pressure Probe ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Group 5 ◽  
Group 2 ◽  
Angiotensin Type

A major proposed mechanism for the initiation of hypertension involves a primary increase in renal tubular sodium (Na+) reabsorption. Activation of intrarenal angiotensin type-2 receptors (AT2R) increases Na+ excretion; however, the role of intrarenal angiotensin type-2 receptors (AT2R) in the development of hypertension is unknown. Sprague-Dawley rats (N=36) underwent uninephrectomy and telemetric blood pressure probe implantation. Following a 72h recovery, two osmotic minipumps were inserted in each rat, one for chronic systemic delivery of 5% dextrose in water (D5W) or angiotensin II (Ang II, 200 ng/kg/min), and one for chronic intrarenal delivery of D5W (0.25 μL/h x 7d), highly selective AT2R agonist Compound 21 (C-21; 60 ng/kg/min x 7d), or specific AT2R antagonist PD-1223319 (PD; 10 ng/kg/min x 7d). Five groups of rats were studied: Group 1 (Control; N=10): systemic D5W + intrarenal D5W; Group 2 (Ang II-induced hypertension; N=8): systemic Ang II + intrarenal D5W; Group 3 (N=6): systemic Ang II + intrarenal C-21; Group 4 (N=6): systemic Ang II + 48h lead-in intrarenal C-21; Group 5 (N=6): systemic Ang II + intrarenal PD. Systemic Ang II infusion increased mean systolic blood pressure from 126±5 to 190±3 mm Hg over a 7d period in Group 2 (ANOVA F=73; P<1 X 10-6). Intrarenal administration of AT2R agonist C-21 (Groups 3 and 4) markedly inhibited the pressor effect of systemic Ang II (P<0.0001). Intrarenal AT2R antagonist PD (Group 5) augmented the pressor action of Ang II (P<0.0001). Consecutive 24h urinary Na+ excretion (UNaV) was reduced from 0.95±0.04 to 0.34±0.07 μmol/min (P<0.0001) on day 1 of Ang II infusion; Ang II-induced antinatriuresis was inhibited by intrarenal C-21 (P<0.0001) and augmented by intrarenal PD (P<0.0001) during the entire 7d infusion, demonstrating that one of the mechanisms to prevent Ang II-induced hypertension during intrarenal AT2R activation is the abolition of the initial increase in Na+ reabsorption that triggers the hypertensive cascade in this model. Thus, renal AT2Rs represent a novel therapeutic target for the prevention of hypertension.

Abstract 095: Human (Pro)renin Receptor Activation Induces an Angiotensin II-Independent Pressor Response Mediated by NADPH Oxidase 4 Activity

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Michelle N Sullivan ◽  
Wencheng Li ◽  
Curt D Sigmund ◽  
Yumei Feng
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Signaling Pathways ◽  
Pressor Response ◽  
Receptor Activation ◽  
Fold Change ◽  
Mrna Levels ◽  
Ang Ii ◽  
Proteolytic Activation ◽  
Nadph Oxidase 4

The binding of prorenin to the (pro)renin receptor (PRR) induces non-proteolytic activation of prorenin and generation of angiotensin II (Ang II). PRR activation can also induce Ang II-independent signaling pathways. However, whether Ang II-independent signaling pathways are critical for blood pressure (BP) regulation is not known. To address this question, we created transgenic mice that overexpress the human PRR (hPRR) selectively in neurons (Syn-hPRR). Activated human prorenin (hPRO) cannot cleave endogenous mouse angiotensinogen to generate Ang II. Therefore, administration of hPRO to Syn-hPRR mice can be used to examine Ang II-independent PRR signaling in BP regulation. Intracerebroventricular (ICV) infusion of hPRO increases BP in Syn-hPRR mice (ΔMAP 23 ± 4.6, n = 4) but has no effect on wildtype (WT) mice (ΔMAP 2 ± 0.8, n = 6). The hPRO-induced pressor response in Syn-hPRR mice is unaffected by co-infusion with the Ang II type 1 receptor blocker losartan (ΔMAP 19 ± 5.2, n = 8), suggesting that the response is independent of Ang II. Interestingly, co-infusion with an inhibitor of the reactive oxygen species-generating enzyme NADPH oxidase (NOX), diphenyleneiodonium, nearly abolishes the hPRO-induced pressor response in Syn-hPRR mice (ΔMAP 4.7 ± 1.0, n = 4), indicating that NOX activity is required. Additionally, we find that basal NOX activity is enhanced in the Syn-hPRR hypothalamus relative to WT mice (1.4 fold change). We next examined which NOX isoform is responsible for the hPRO-induced pressor response and enhanced activity. NOX4 mRNA levels are greater (2.7 ± 0.6 fold change), but NOX1 (1.2 ± 0.3 fold change) and NOX2 (1.2 ± 0.3 fold change) mRNA levels are not different, in the hypothalamus of Syn-hPRR compared to WT mice (n = 3). Adenovirus-mediated delivery of NOX2, NOX4, or a scrambled sequence shRNA was ICV injected in Syn-hPRR mice. After 7 days, we found that treatment with NOX2 (ΔMAP 20 ± 5.2) or scrambled (ΔMAP 23 ± 3.2) shRNA had no effect on the hPRO-induced pressor response (n = 5). However, the hPRO-induced increase in BP is attenuated in Syn-hPRR mice injected with NOX4 shRNA (ΔMAP 5.9 ± 2.8). Together, these data indicate that NOX4 mediates the Ang II-independent pressor response to activation of the human (pro)renin receptor in Syn-hPRR mice.

Molecular mechanism of ADP-ribosyl cyclase activation in angiotensin II signaling in murine mesangial cells

2008 ◽  
Vol 294 (4) ◽  
pp. F982-F989 ◽  
Author(s):  
Seon-Young Kim ◽  
Rukhsana Gul ◽  
So-Young Rah ◽  
Suhn Hee Kim ◽  
Sung Kwang Park ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Tyrosine Kinase ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
Dependent Manner ◽  
Ang Ii ◽  
Akt Phosphorylation ◽  
Cyclase Activation ◽  
Adp Ribosyl Cyclase ◽  
Phosphoinositide 3 Kinase

ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca2+-mobilizing second messenger cyclic ADP-ribose (cADPR) from NAD+. In this study, we investigated the molecular basis of ADPR-cyclase activation and the following cellular events in angiotensin II (ANG II) signaling in mouse mesangial cells (MMCs). Treatment of MMCs with ANG II induced an increase in intracellular Ca2+ concentrations through a transient Ca2+ release via an inositol 1,4,5-trisphosphate receptor and a sustained Ca2+ influx via L-type Ca2+ channels. The sustained Ca2+ signal, but not the transient Ca2+ signal, was blocked by a cADPR antagonistic analog, 8-bromo-cADPR (8-Br-cADPR), and an ADPR-cyclase inhibitor, 4,4′-dihydroxyazobenzene (DHAB). In support of the results, ANG II stimulated cADPR production in a time-dependent manner, and DHAB inhibited ANG II-induced cADPR production. Application of pharmacological inhibitors revealed that activation of ADPR-cyclase by ANG II involved ANG II type 1 receptor, phosphoinositide 3-kinase, protein tyrosine kinase, and phospolipase C-γ1. Moreover, DHAB as well as 8-Br-cADPR abrogated ANG II-mediated Akt phosphorylation, nuclear translocation of nuclear factor of activated T cell, and uptake of [3H]thymidine and [3H]leucine in MMCs. These results demonstrate that ADPR-cyclase in MMCs plays a pivotal role in ANG II signaling for cell proliferation and protein synthesis.

scholarly journals Presynaptic Angiotensin II AT1 Receptors Enhance Inhibitory and Excitatory Synaptic Neurotransmission to Motoneurons and Other Ventral Horn Neurons in Neonatal Rat Spinal Cord

2005 ◽  
Vol 94 (2) ◽  
pp. 1405-1412 ◽  
Author(s):  
Murat Oz ◽  
Keun-Hang Yang ◽  
Michael J. O'Donovan ◽  
Leo P. Renaud
Keyword(s):  
Spinal Cord ◽  
Angiotensin Ii ◽  
Ventral Horn ◽  
Synaptic Activity ◽  
Neonatal Rat ◽  
Ang Ii ◽  
Synaptic Neurotransmission ◽  
Excitatory Neurotransmission ◽  
Ventral Spinal Cord

In neonatal spinal cord, we previously reported that exogenous angiotensin II (ANG II) acts at postsynaptic AT1 receptors to depolarize neonatal rat spinal ventral horn neurons in vitro. This study evaluated an associated increase in synaptic activity. Patch clamp recordings revealed that 38/81 thoracolumbar (T7–L5) motoneurons responded to bath applied ANG II (0.3–1 μM; 30 s) with a prolonged (5–10 min) and reversible increase in spontaneous postsynaptic activity, selectively blockable with Losartan ( n = 5) but not PD123319 ( n = 5). ANG-II-induced events included both spontaneous inhibitory (IPSCs; n = 6) and excitatory postsynaptic currents (EPSCs; n = 5). While most ANG induced events were tetrodotoxin-sensitive, ANG induced a significant tetrodotoxin-resistant increase in frequency but not amplitude of miniature IPSCs ( n = 7/13 cells) and EPSCs ( n = 2/7 cells). In 35/77 unidentified neurons, ANG II also induced a tetrodotoxin-sensitive and prolonged increase in their spontaneous synaptic activity that featured both IPSCs ( n = 5) and EPSCs ( n = 4) when tested in the presence of selective amino acid receptor antagonists. When tested in the presence of tetrodotoxin, ANG II was noted to induce a significant increase in the frequency but not the amplitude of mIPSCs ( n = 9) and mEPSCs ( n = 8). ANG also increased spontaneous motor activity from isolated mouse lumbar ventral rootlets. Collectively, these observations support the existence of a wide pre- and postsynaptic distribution of ANG II AT1 receptors in neonatal ventral spinal cord that are capable of influencing both inhibitory and excitatory neurotransmission.

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