Anti-calmodulin agents affect osmotic and angiotensin II-induced vasopressin release

1989 ◽  
Vol 256 (4) ◽  
pp. E516-E523 ◽  
Author(s):  
N. F. Rossi ◽  
R. W. Schrier
Keyword(s):  
Angiotensin Ii ◽  
Calcium Ions ◽  
Calcium Influx ◽  
Alternative Mechanism ◽  
Hormone Release ◽  
Ang Ii ◽  
Vasopressin Release ◽  
Blocking Effects ◽  
Osmotic Stimulation ◽  
Crucial Part

Calcium ions and particularly calcium influx play a crucial part in initiating the intracellular events that result in arginine vasopressin (AVP) release to both osmotic and nonosmotic stimuli. Calmodulin appears to modulate the effects of calcium on synaptic transmission and hormone release in other systems. This study tested the effects of three distinct classes of anti-calmodulin agents on the release of AVP to either a rise in osmolality of 20 mosmol/kg water or to 1 X 10(-5) angiotensin II (ANG II) in cultured hypothalamo-neurohypophysical complexes. Micromolar concentrations of R 24571, the active naphthalenesulfonamides, W 7 and W 13, and trifluoperazine (TFP) inhibited AVP release to osmotic stimulation. In contrast, W 5, a severalfold less active anti-calmodulin agent, had no effect on osmotically stimulated AVP release. The active naphthalenesulfonamides, but not R 24571 or TFP, blocked release of AVP to ANG II. In contrast, neither R 24571 nor TFP inhibited AVP release to ANG II stimulation. Collectively, the data demonstrated a dissociation between inhibition of AVP release and the anti-calmodulin properties of the drugs, thereby suggesting that nonspecific actions masked the calmodulin-blocking effects of the drugs or that the inhibition occurred by some alternative mechanism(s).

scholarly journals Angiotensin II induces membrane trafficking of natively expressed transient receptor potential vanilloid type 4 channels in hypothalamic 4B cells

2014 ◽  
Vol 307 (8) ◽  
pp. R945-R955 ◽  
Author(s):  
Ashwini Saxena ◽  
Martha Bachelor ◽  
Yong H. Park ◽  
Flavia R. Carreno ◽  
T. Prashant Nedungadi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Membrane Trafficking ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Src Kinase ◽  
Receptor Potential ◽  
Family Type ◽  
Transient Receptor Potential Vanilloid ◽  
Ang Ii ◽  
Transient Receptor

Transient receptor potential vanilloid family type 4 (TRPV4) channels are expressed in central neuroendocrine neurons and have been shown to be polymodal in other systems. We previously reported that in the rodent, a model of dilutional hyponatremia associated with hepatic cirrhosis, TRPV4 expression is increased in lipid rafts from the hypothalamus and that this effect may be angiotensin dependent. In this study, we utilized the immortalized neuroendocrine rat hypothalamic 4B cell line to more directly test the effects of angiotensin II (ANG II) on TRPV4 expression and function. Our results demonstrate the expression of corticotropin-releasing factor (CRF) transcripts, for sex-determining region Y (SRY) (male genotype), arginine vasopressin (AVP), TRPV4, and ANG II type 1a and 1b receptor in 4B cells. After a 1-h incubation in ANG II (100 nM), 4B cells showed increased TRPV4 abundance in the plasma membrane fraction, and this effect was prevented by the ANG II type 1 receptor antagonist losartan (1 μM) and by a Src kinase inhibitor PP2 (10 μM). Ratiometric calcium imaging experiments demonstrated that ANG II incubation potentiated TRPV4 agonist (GSK 1016790A, 20 nM)-induced calcium influx (control 18.4 ± 2.8% n = 5 and ANG II 80.5 ± 2.4% n = 5). This ANG II-induced increase in calcium influx was also blocked by 1 μM losartan and 10 μM PP2 (losartan 26.4 ± 3.8% n = 5 and PP2 19.7 ± 3.9% n = 5). Our data suggests that ANG II can increase TRPV4 channel membrane expression in 4B cells through its action on AT1R involving a Src kinase pathway.

Actions of calcium ions and a calcium-influx blocker on basal and TRH- and GnRH-stimulated hormone release in patients with pituitary adenomas

1987 ◽  
Vol 10 (5) ◽  
pp. 427-433 ◽  
Author(s):  
M. Davis ◽  
B. Nassberg ◽  
J. L. C. Borges ◽  
A. Iranmanesh ◽  
G. Lizzaralde ◽  
...  
Keyword(s):  
Calcium Ions ◽  
Pituitary Adenomas ◽  
Calcium Influx ◽  
Hormone Release

scholarly journals Nucleus of the solitary tract lesions enhance drinking, but not vasopressin release, induced by angiotensin

2000 ◽  
Vol 279 (1) ◽  
pp. R239-R247 ◽  
Author(s):  
Ann M. Schreihofer ◽  
Edward M. Stricker ◽  
Alan F. Sved
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Ang Ii ◽  
Solitary Tract ◽  
Neural Signals ◽  
Vasopressin Release ◽  
Osmotic Stimulation ◽  
Higher Doses ◽  
Conscious Control ◽  
Stimulation Of

Rats with chronic nucleus of the solitary tract lesions (NTS-X) drink water and release vasopressin (VP) in response to reduced blood volume despite an absence of neural signals from cardiac and arterial baroreceptors. The present study determined whether rats with NTS-X have a greater sensitivity to circulating ANG II, which may contribute to the drinking and VP responses to hypovolemia. In conscious control rats and rats with NTS-X, ANG II was infused intravenously for 1 h at 10, 100, or 250 ng · kg−1 · min−1. At the two higher doses, ANG II stimulated more water intake with a shorter latency to drink in rats with NTS-X than in control rats. In contrast, infusion of ANG II produced comparable increases in plasma VP in the two groups. At the two higher doses, ANG II produced an enhanced increase in arterial pressure (AP) in rats with NTS-X, and the bradycardia seen in control rats was reversed to a tachycardia. Infusion of hypertonic saline, which did not alter AP or heart rate, produced comparable drinking and VP release in the two groups. These results demonstrate that chronic NTS-X increases the dipsogenic response of rats to systemic ANG II but has no effect on ANG II-induced VP release or the osmotic stimulation of these responses.

Calcium influx and intracellular stores in angiotensin II stimulation of normal and hyperplastic pituitary cells

1999 ◽  
Vol 277 (3) ◽  
pp. E455-E463 ◽  
Author(s):  
Arturo Gonzalez Iglesias ◽  
Graciela Diaz-Torga ◽  
Victoria Lux-Lantos ◽  
Carlos Libertun ◽  
Damasia Becu-Villalobos
Keyword(s):  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Calcium Influx ◽  
Pituitary Cells ◽  
Ang Ii ◽  
Rat Pituitary ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Ca ◽  
Rat Pituitary Cells ◽  
Stimulation Of

In rat pituitary cells from estrogen-induced hyperplasia, angiotensin II (ANG II) does not evoke a clear spike elevation of intracellular Ca2+concentration ([Ca2+]i) but induces a plateau increase. The present work was undertaken to establish whether this difference was related to a differential participation of intracellular and/or plasma membrane Ca2+ channels. We first tested the effect of 10 nM ANG II on [Ca2+]iin the absence of extracellular Ca2+ in cells depolarized with 25 mM K+ or in the presence of blockers of L-type voltage-sensitive Ca2+ channels (VSCC). These treatments did not alter spike elevation in [Ca2+]iin controls but reduced plateau levels in hyperplastic cells. Intracellular Ca2+ stores were similar in both groups, as assessed by thapsigargin treatment, but this drug abolished spike increase in controls and scarcely modified plateau levels in hyperplastic cells. Finally, inositol trisphosphate (InsP3) production in response to ANG II was significantly higher in control cells. We conclude that the observed plateau rise in hyperplastic cells results mainly from Ca2+ influx through VSCC. In contrast, in control cells, the ANG II-induced spike increase in [Ca2+]iresults from mobilization of Ca2+from thapsigargin-sensitive internal channels, activated by higher inositol 1,4,5-trisphosphate generation.

Involvement of central angiotensin II type 1 receptors in LPS-induced systemic vasopressin release and blood pressure regulation in rats

2009 ◽  
Vol 106 (6) ◽  
pp. 1943-1948 ◽  
Author(s):  
Fumihiro Shimizu ◽  
Toshihiro Kasai ◽  
Akira Takamata
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Plasma Osmolality ◽  
Blood Pressure Regulation ◽  
Ang Ii ◽  
Pressure Regulation ◽  
Vasopressin Release ◽  
Captopril Treatment

The purpose of this study was to evaluate the involvement of central angiotensin II (ANG II) and ANG II type 1 (AT1) receptors in systemic release of arginine vasopressin (AVP) and blood pressure regulation during endotoxemia. LPS (150 μg/kg) was injected intravenously 30 min after intracerebroventricular (icv) losartan (50 μg), an AT1 receptor antagonist, or subcutaneous (sc) captopril (50 mg/kg), an angiotensin-converting enzyme inhibitor. Rats with icv and sc saline injections served as control. LPS administration increased plasma AVP concentration from 2.1 ± 0.2 to 15.2 ± 2.5 pg/ml (60 min after LPS injection) without significant changes in plasma osmolality or hematocrit. LPS-induced AVP secretion was significantly attenuated by pretreatment with icv losartan (2.3 ± 0.5 to 3.7 ± 0.5 pg/ml) but was not attenuated after peripheral captopril treatment (2.2 ± 0.6 to 17.6 ± 4.2 pg/ml). LPS administration significantly decreased systolic blood pressure (SBP) by 22.7 ± 5.4 mmHg after intravenous LPS injection in icv losartan-treated rats, while SBP remained unchanged in vehicle-treated or sc captopril-treated rats by intravenous LPS. These results indicate that central AT1 receptors, not responsive to peripheral ANG II, play an important role in systemic AVP secretion and maintenance of blood pressure during endotoxemia.

scholarly journals AT1 and AT2 receptors modulate renal tubular cell necroptosis in angiotensin II-infused renal injury mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yongjun Zhu ◽  
Hongwang Cui ◽  
Jie Lv ◽  
Haiqin Liang ◽  
Yanping Zheng ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Critical Role ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Renal Tubular Cell ◽  
Ang Ii ◽  
Renal Tubular

AbstractAbnormal renin-angiotensin system (RAS) activation plays a critical role in the initiation and progression of chronic kidney disease (CKD) by directly mediating renal tubular cell apoptosis. Our previous study showed that necroptosis may play a more important role than apoptosis in mediating renal tubular cell loss in chronic renal injury rats, but the mechanism involved remains unknown. Here, we investigate whether blocking the angiotensin II type 1 receptor (AT1R) and/or angiotensin II type 2 receptor (AT2R) beneficially alleviates renal tubular cell necroptosis and chronic kidney injury. In an angiotensin II (Ang II)-induced renal injury mouse model, we found that blocking AT1R and AT2R effectively mitigates Ang II-induced increases in necroptotic tubular epithelial cell percentages, necroptosis-related RIP3 and MLKL protein expression, serum creatinine and blood urea nitrogen levels, and tubular damage scores. Furthermore, inhibition of AT1R and AT2R diminishes Ang II-induced necroptosis in HK-2 cells and the AT2 agonist CGP42112A increases the percentage of necroptotic HK-2 cells. In addition, the current study also demonstrates that Losartan and PD123319 effectively mitigated the Ang II-induced increases in Fas and FasL signaling molecule expression. Importantly, disruption of FasL significantly suppressed Ang II-induced increases in necroptotic HK-2 cell percentages, and necroptosis-related proteins. These results suggest that Fas and FasL, as subsequent signaling molecules of AT1R and AT2R, might involve in Ang II-induced necroptosis. Taken together, our results suggest that Ang II-induced necroptosis of renal tubular cell might be involved both AT1R and AT2R and the subsequent expression of Fas, FasL signaling. Thus, AT1R and AT2R might function as critical mediators.

Pharmacological blockage of ICAM-1 improves angiotensin II-induced cardiac remodeling by inhibiting adhesion of LFA-1+ monocytes

2019 ◽  
Vol 317 (6) ◽  
pp. H1301-H1311 ◽  
Author(s):  
Qiu-Yue Lin ◽  
Ping-Ping Lang ◽  
Yun-Long Zhang ◽  
Xiao-Lei Yang ◽  
Yun-Long Xia ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Adhesion Molecules ◽  
Vascular Endothelium ◽  
Cardiac Remodeling ◽  
Leukocyte Adhesion ◽  
Neutralizing Antibody ◽  
Ang Ii ◽  
Cardiac Contractile ◽  
And Migration

Intercellular adhesion molecule-1 (ICAM-1) is a member of an immunoglobulin-like superfamily of adhesion molecules that mediate leukocyte adhesion to vascular endothelium and are involved in several cardiovascular diseases, including ischemia-reperfusion injury, myocardial infarction, and atherosclerosis. However, the role of ICAM-1 in angiotensin II (ANG II)-induced cardiac remodeling in mice remains unclear. Wild-type mice were administered an IgG control or ICAM-1 neutralizing antibody (1 and 2 mg/mouse, respectively) and ANG II (1,000 ng·kg−1·min−1) for up to 14 days. Cardiac contractile function and structure were detected by echocardiography. Hypertrophy, fibrosis, and inflammation were assessed by histological examination. The infiltration of lymphocyte function-associated antigen-1 (LFA-1+) monocytes/macrophages was assessed by immunostaining. The mRNA expression of genes was evaluated by quantitative RT-PCR analysis. Protein levels were tested by immunoblotting. We found that ICAM-1 expression in ANG II-infused hearts and ICAM-1 levels in serum from human patients with heart failure were significantly increased. Moreover, ANG II infusion markedly enhanced ANG II-induced hypertension, caused cardiac contractile dysfunction, and promoted cardiac hypertrophy, fibrosis, and LFA-1+ macrophage infiltration. Conversely, blockage of ICAM-1 with a neutralizing antibody dose-dependently attenuated these effects. Moreover, our in vitro data further demonstrated that blocking ICAM-1 inhibited ANG II-induced LFA-1+ macrophage adhesion to endothelial cells and migration. In conclusion, these results provide novel evidence that blocking ICAM-1 exerts a protective effect in ANG II-induced cardiac remodeling at least in part through the modulation of adhesion and infiltration of LFA-1+ macrophages in the heart. Inhibition of ICAM-1 may represent a new therapeutic approach for hypertrophic heart diseases. NEW & NOTEWORTHY Leukocyte adhesion to vascular endothelium is a critical step in cardiovascular diseases. ICAM-1 is a member of immunoglobulin-like superfamily of adhesion molecules that binds LFA-1 to mediate leukocytes adhesion and migration. However, the significance of ICAM-1 in ANG II-induced cardiac remodeling remains unclear. This study reveals that blocking of ICAM-1 prevents ANG II-induced cardiac remodeling via modulating adhesion and migration of LFA-1+ monocytes, may serve as a novel therapeutic target for hypertensive cardiac diseases.

scholarly journals Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli

2010 ◽  
Vol 298 (1) ◽  
pp. F177-F186 ◽  
Author(s):  
Anne D. M. Riquier-Brison ◽  
Patrick K. K. Leong ◽  
Kaarina Pihakaski-Maunsbach ◽  
Alicia A. McDonough
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Enzyme Inhibitor ◽  
Volume Flow Rate ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Water Reabsorption ◽  
Associated Proteins ◽  
Gradient Fractionation

Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water reabsorption. We showed that treating rats acutely with the angiotensin-converting enzyme inhibitor captopril decreases PT salt and water reabsorption and provokes rapid redistribution of the Na+/H+ exchanger isoform 3 (NHE3), Na+/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli. The aim of the present study was to determine whether acute ANG II infusion increases the abundance of PT NHE3, NaPi2, and associated proteins in the microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused with a dose of captopril (12 μg/min for 20 min) that increased PT flow rate ∼20% with no change in blood pressure (BP) or glomerular filtration rate (GFR). When ANG II (20 ng·kg−1·min−1 for 20 min) was added to the captopril infusate, PT volume flow rate returned to baseline without changing BP or GFR. After captopril, NHE3 was localized to the base of the microvilli and NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2 redistributed into the microvilli, assayed by confocal microscopy and density gradient fractionation. Additional PT proteins that redistributed into low-density microvilli-enriched membranes in response to ANG II included myosin VI, DPPIV, NHERF-1, ezrin, megalin, vacuolar H+-ATPase, aminopeptidase N, and clathrin. In summary, in response to 20 min ANG II in the absence of a change in BP or GFR, multiple proteins traffic into the PT brush-border microvilli where they likely contribute to the rapid increase in PT salt and water reabsorption.

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.

Angiotensin II regulates nephrogenesis and renal vascular development

1995 ◽  
Vol 269 (1) ◽  
pp. F110-F115 ◽  
Author(s):  
A. Tufro-McReddie ◽  
L. M. Romano ◽  
J. M. Harris ◽  
L. Ferder ◽  
R. A. Gomez
Keyword(s):  
Angiotensin Ii ◽  
Kidney Development ◽  
Rana Catesbeiana ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Ang Ii ◽  
Newborn Rats ◽  
Sprague Dawley ◽  
Renal Growth ◽  
Glomerular Size ◽  
Renal Vascular

To test the hypothesis that angiotensin II (ANG II) is necessary for normal embryonic and postnatal kidney development, the effect of angiotensin receptor blockade or angiotensin converting enzyme inhibition on nephrovascular development was studied in newborn Sprague-Dawley rats and in Rana catesbeiana tadpoles undergoing prometamorphosis. Blockade of ANG II type 1 receptor (AT1) in newborn rats induced an arrest in nephrovascular maturation and renal growth, resulting in altered kidney architecture, characterized by fewer, thicker, and shorter afferent arterioles, reduced glomerular size and number, and tubular dilatation. Inhibition of ANG II generation in tadpoles induced even more marked developmental renal abnormalities. Blockade of ANG II type 2 receptor (AT2) in newborn rats did not alter renal growth or morphology. Results indicate that ANG II regulates nephrovascular development, a role that is conserved across species.

Sign in / Sign up

Export Citation Format

Share Document