Angiotensin II overflow from canine skeletal muscle in vivo: importance of plasma angiotensin I

1994 ◽  
Vol 266 (5) ◽  
pp. R1664-R1669 ◽  
Author(s):  
J. H. Schwieler ◽  
J. Nussberger ◽  
T. Kahan ◽  
P. Hjemdahl
Keyword(s):  
De Novo ◽  
Ex Vivo ◽  
Plasma Renin ◽  
Gracilis Muscle ◽  
Ang Ii ◽  
Concentration Difference ◽  
Beta Adrenoceptor ◽  
Arterial Blood ◽  
Catheter System

The overflows (i.e., veno-arterial concentration differences multiplied by plasma flow) of angiotensin-(1-10) decapeptide (ANG I) and angiotensin-(1-8) octapeptide (ANG II) from blood-perfused canine gracilis muscle in situ were studied. Special precautions were taken to minimized ex vivo generation and/or degradation of angiotensins in the sampled blood. ANG I was found to be generated in the catheter system supplying the gracilis muscle with arterial blood, but plasma renin activity and ANG II levels were uninfluenced by the catheter system. A positive venoarterial concentration difference over the muscle itself was found for ANG II but not for ANG I under basal conditions. Isoprenaline elicited vasodilatation, reduced ANG I overflow, and tended to increase ANG II overflow, whereas beta-adrenoceptor blockade by propranolol had no effect on these variables. In conclusion, we found no evidence for a local de novo synthesis of ANG II from the gracilis muscle vasculature in vivo. The net overflow of ANG II was most likely caused by local conversion in the tissue of ANG I artifactually generated in the arterial catheter system. beta-Adrenoceptor stimulation enhanced the local conversion of ANG I to ANG II, probably by exposing a greater endothelial surface containing angiotensin-converting enzyme activity.

scholarly journals A fluorogenic near-infrared imaging agent for quantifying plasma and local tissue renin activity in vivo and ex vivo

2012 ◽  
Vol 303 (4) ◽  
pp. F593-F603 ◽  
Author(s):  
Jun Zhang ◽  
Dorin V. Preda ◽  
Kristine O. Vasquez ◽  
Jeff Morin ◽  
Jeannine Delaney ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Near Infrared ◽  
Ex Vivo ◽  
Kidney Tissue ◽  
Plasma Renin ◽  
Renin Activity ◽  
Imaging Agent ◽  
Ang Ii

The renin-angiotensin system (RAS) is well studied for its regulation of blood pressure and fluid homeostasis, as well as for increased activity associated with a variety of diseases and conditions, including cardiovascular disease, diabetes, and kidney disease. The enzyme renin cleaves angiotensinogen to form angiotensin I (ANG I), which is further cleaved by angiotensin-converting enzyme to produce ANG II. Although ANG II is the main effector molecule of the RAS, renin is the rate-limiting enzyme, thus playing a pivotal role in regulating RAS activity in hypertension and organ injury processes. Our objective was to develop a near-infrared fluorescent (NIRF) renin-imaging agent for noninvasive in vivo detection of renin activity as a measure of tissue RAS and in vitro plasma renin activity. We synthesized a renin-activatable agent, ReninSense 680 FAST (ReninSense), using a NIRF-quenched substrate derived from angiotensinogen that is cleaved specifically by purified mouse and rat renin enzymes to generate a fluorescent signal. This agent was assessed in vitro, in vivo, and ex vivo to detect and quantify increases in plasma and kidney renin activity in sodium-sensitive inbred C57BL/6 mice maintained on a low dietary sodium and diuretic regimen. Noninvasive in vivo fluorescence molecular tomographic imaging of the ReninSense signal in the kidney detected increased renin activity in the kidneys of hyperreninemic C57BL/6 mice. The agent also effectively detected renin activity in ex vivo kidneys, kidney tissue sections, and plasma samples. This approach could provide a new tool for assessing disorders linked to altered tissue and plasma renin activity and to monitor the efficacy of therapeutic treatments.

Abstract 290: Haemogenic Endocardium Contribute To Definitive Hematopoiesis During Cardiogenesis

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Haruko Nakano ◽  
Xiaoqian Liu ◽  
Armin Arshi ◽  
Ben van Handel ◽  
Rajkumar Sasidharan ◽  
...  
Keyword(s):  
De Novo ◽  
Ex Vivo ◽  
Embryonic Stem ◽  
Circulatory System ◽  
Lineage Tracing ◽  
Mouse Heart ◽  
Heart Tube ◽  
Cardiac Progenitors ◽  
Definitive Hematopoiesis

The circulatory system is the first functional organ system that develops during mammalian life. Accumulating evidences suggest that cardiac and endocardial cells can arise from a single common progenitor cell during mammalian cardiogenesis. Notably, these early cardiac progenitors express multiple hematopoietic transcription factors, consistent with previous reports. Indeed, a close relationship among cardiac, endocardial and hematopoietic lineages has been suggested in fly, zebrafish, and embryonic stem cell in vitro differentiation models. However, it is unclear when, where and how this hematopoietic gene program is in operation during in vivo mammalian cardiogenesis. Hematopoietic colony assay suggests that mouse heart explants generate myeloids and erythroids in the absence of circulation, suggesting that the heart tube is a de novo site for the definitive hematopoiesis. Lineage tracing revealed that putative cardiac-derived Nkx2-5+/Isl1+ endocardial cells give rise to CD41+ hematopoietic progenitors that contribute to definitive hematopoiesis in vivo and ex vivo during embryogenesis earlier than in the AGM region. Furthermore, Nkx2-5 and Isl1 are both required for the hemogenic activity of the endocardium. Together, identification of Nkx2-5/Isl1-dependent hemogenic endocardial cells (1) adds hematopoietic component in the cardiogenesis lineage tree, (2) changes the long-held dogma that AGM is the only major source of definitive hematopoiesis in the embryo proper, and (3) represents phylogenetically conserved fundamental mechanism of cardio-vasculo-hematopoietic differentiation pathway during the development of circulatory system.

Salt-sensitive hypertension in ANP knockout mice is prevented by AT1 receptor antagonist losartan

1999 ◽  
Vol 277 (3) ◽  
pp. R624-R630 ◽  
Author(s):  
Luis G. Melo ◽  
Anthony T. Veress ◽  
Chee K. Chong ◽  
Uwe Ackermann ◽  
Harald Sonnenberg
Keyword(s):  
Receptor Antagonist ◽  
Knockout Mice ◽  
Plasma Renin ◽  
Plasma Catecholamine ◽  
Ang Ii ◽  
Dietary Salt ◽  
Water Control ◽  
Dietary Regimen ◽  
Arterial Blood ◽  
Salt Sensitive Hypertension

Mice harboring a functional deletion of the pro-atrial natriuretic peptide (ANP) gene (−/−) develop salt-sensitive hypertension relative to their wild-type (+/+) counterparts after prolonged (>1 wk) maintenance on high-salt (HS, 8% NaCl) diet. We reported recently that the sensitization of arterial blood pressure (ABP) to dietary salt in the −/− mice is associated with failure to downregulate plasma renin activity. To further characterize the role and mechanism of ANG II in the sensitization of ABP to salt in the ANP “knockout” mice, we measured ABP, heart rate (HR), and plasma catecholamine and aldosterone concentrations in −/− and +/+ mice maintained on HS for 4 wk and treated with daily injections of AT1 receptor antagonist DuP-753 (losartan) or distilled water (control). Daily food and water intake and fluid and electrolyte excretion were also measured during the first and last weeks of the dietary regimen. Cumulative urinary excretion of fluid and electrolytes did not differ significantly between genotypes and was not altered by chronic treatment with losartan. Basal ABP and HR were significantly elevated in control −/− mice compared with control +/+ mice. Losartan did not affect ABP or HR in +/+ mice, but reduced ABP and HR in the −/− mice to the levels in the +/+ mice. Total plasma catecholamine was elevated by approximately ten-fold in control −/− mice compared with control +/+ mice. Losartan reduced plasma catecholamine concentration significantly in −/− mice and abrogated the difference in plasma catecholamine between −/− and +/+ mice on HS diet. Plasma aldosterone did not differ significantly between genotypes and was not altered by losartan. We conclude that salt sensitivity of ABP in ANP knockout mice is mediated, at least in part, by a synergistic interaction between ANG II and sympathetic nerve activity.

Abstract 249: Delayed Gene Transfer Increases Transgene Expression in Vein Grafts

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Liang Du ◽  
Jingwan Zhang ◽  
Alexander Clowes ◽  
David Dichek
Keyword(s):  
Gene Expression ◽  
Blood Flow ◽  
Gene Transfer ◽  
Transgene Expression ◽  
Ex Vivo ◽  
Arterial Blood Flow ◽  
Vein Grafts ◽  
Arterial Blood ◽  
En Face

Background Autogenous vein grafts are effective therapies for obstructive arterial disease. However, their long-term utility is limited by stenosis and occlusion. Genetic engineering of veins that prevents intimal hyperplasia and atherosclerosis could significantly improve the clinical utility of vein grafts. We recently reported that a helper-dependent adenoviral vector (HDAd) reduces atherosclerosis 4 wks after gene transfer in fat-fed rabbits and can express a therapeutic transgene (apo AI) in normal rabbit carotids for at least 48 wks. Use of HDAd for vein graft gene therapy will depend on achievement of similarly high and persistent transgene expression in grafted veins. Hypothesis We tested the hypothesis that Ad-mediated transgene expression in grafted veins (at an early time point) can be increased by varying the timing of gene transfer. Methods Rabbit external jugular veins were transduced by exposure to a beta galactosidase (b-gal)-expressing Ad: in situ either without (a) or with (b) immediate arterial grafting; c) ex vivo with grafting after overnight incubation with Ad; d) in vivo immediately after grafting and e) in vivo 4 wks after grafting (n = 6 - 19 veins/group). Transgene expression was measured in veins removed 3 d after Ad exposure by PCR quantitation of b-gal mRNA and by en-face planimetry of blue-stained area. Results B-gal transgene expression was higher in ungrafted veins than in veins grafted immediately after gene transfer (84 ± 17 vs 9.4 ± 2.0 arbitrary units (AU); P < 0.0001). Overnight incubation of veins with Ad increased gene expression ex vivo by 10-fold but neither this nor performing vector infusion immediately after grafting improved gene expression (11 ± 4.7 and 9.1 ± 1.8 AU; P > 0.9 for both vs immediately grafted veins). Delaying gene transfer until 4 wks after grafting significantly increased gene expression, to a level equivalent to transgene expression in ungrafted veins (61 ± 11 AU; P = 0.3 vs ungrafted veins). En face planimetry yielded similar results. Conclusions Exposure of a transduced vein to arterial blood flow is associated with significant loss of transgene expression. Transgene expression in grafted veins is significantly higher when gene transfer is performed 4 wks after exposure of the vein to arterial blood flow.

Abstract 257: Oxidative Stress Induces Endothelial Dysfunction: Role of Ubiquitin-Proteasome System

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jian Xu ◽  
Shuangxi Wang ◽  
Yong Wu ◽  
Ping Song ◽  
Miao Zhang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
De Novo ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Proteasome Inhibitors ◽  
Dominant Negative ◽  
26S Proteasome ◽  
No Production ◽  
Ang Ii ◽  
Enos Uncoupling

Endothelial Nitric oxide (NO) production is dependent on adequate cellular tetrahydrobiopterin (BH 4 ), a key cofactor for endothelial NO syntheses (eNOS). Reduction of BH 4 levels is reported in diseased vessels and plays a causal role in the development of eNOS uncoupling. However, the mechanisms that lead to BH 4 reduction are not entirely understood. Here we report that angiotensin-II (Ang II) reduced tetrahydrobiopterin (BH 4 ) and eNOS uncoupling by peroxynitrite ONOO − )-triggered proteasome activation. Compared to control, exposure of human umbilical vein endothelial cells (HUVEC) to angiotensin II (Ang II, 100nM) for 6h significantly decreased the levels of total biopterins (BH 4 plus BH 2 ) and BH 4 (−22.0 4.6%, n= 3, p<0.01), indicating decreased synthesis of biopterins. In parallel, Ang II but not vehicle significantly reduced the levels of GTP-cyclohydrolase (GTPCH), a rate-limiting enzyme for de novo synthesis of biopterins, and dihydrofolate reductase (DHFR), a crucial enzyme for BH 4 recycle from BH 2 . Ang II but not vehicle significantly increased the 26S proteasome activity. In addition, administration of proteasome inhibitors, MG132, abolished the Ang II-induced reduction of both GTPCH and DHFR. While Ang II significantly increased O 2 − , the scavenging of O 2 − by Tempol (SOD mimetic), or inhibition of NOS with N -nitro-L-arginine methyl ester hydrochloride (L-NAME) (1mM) significantly attenuated Ang II-induced both 26S proteasome activation and the reduction of both GTPCH and DHFR, suggesting that Ang II via endogenous ONOO − causes 26S proteasome-dependent degradation of both GTPCH and DHFR. Moreover, inhibition of NAD(P)H oxidase with either apocynin or by overexpression of p67 phox -dominant negative mutants ablated Ang II-induced proteasome activation and degradation of both GTPCH and DHFR. Finally, treatment of mice aorta ex vivo with MG132 (0.5 μM for 1h followed by Ang II for 12h) reversed the Ang II-induced reduction of GTPCH, DHFR and BH 4 , and increased acetylcholine-induced endothelium-dependent relaxation. We conclude that Ang II activates NAD(P)H oxidase to release O 2 . − and ONOO − , which activate 26S proteasome resulting in increased degradation of both GTPCH and DHFR, two key enzymes in controlling the levels of BH 4 .

scholarly journals The Influence of the Spleen on Neutrophil Apoptosis in Vivo

2011 ◽  
Vol 4 ◽  
pp. JCD.S6444 ◽  
Author(s):  
Jessica F. White ◽  
Andrew S. Cowburn ◽  
Charlotte Summers ◽  
Karen A. Cadwallader ◽  
Iain Mackenzie ◽  
...  
Keyword(s):  
High Efficiency ◽  
Ex Vivo ◽  
Annexin V ◽  
Neutrophil Apoptosis ◽  
Residence Times ◽  
Arterial Blood ◽  
Age Dependent ◽  
Peripheral Arterial ◽  
Random Removal

In contrast to radiolabelled erythrocytes and platelets, radiolabelled neutrophils leave the circulating blood in an exponential manner, indicating random rather than age-dependent removal. Neutrophils transit the spleen with a range of residence times that are log normally distributed. We hypothesized that neutrophils are conditioned to undergo apoptosis to an extent that depends on their intrasplenic residence time and that this provides an explanation for the random removal of these cells from blood. Splenic venous and peripheral arterial blood was sampled simultaneously during abdominal surgery in four patients and age-dependent apoptosis assessed in whole blood using annexin V/PI staining. Apoptosis increased after 4 and 20 h ex-vivo incubation and was invariably higher in splenic venous vs arterial neutrophils. Transit through the spleen appears to promote neutrophil apoptosis, with subsequent high efficiency clearance by the liver. This may explain the mechanism underlying the random removal of neutrophils from the blood.

scholarly journals Inhibition of Autism-Related Crm1 Disrupts Mitosis and Induces Apoptosis of the Cortical Neural Progenitors

2020 ◽  
Vol 30 (7) ◽  
pp. 3960-3976
Author(s):  
Xue Li ◽  
Yue Feng ◽  
Meifang Yan ◽  
Xiaomeng Tu ◽  
Bin Xie ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
De Novo ◽  
Ex Vivo ◽  
Brain Slices ◽  
Neural Progenitors ◽  
Embryonic Brain ◽  
Mitotic Slippage ◽  
Developing Mouse Brain

Abstract De novo microdeletion of chromosome 2p15–16.1 presents clinically recognizable phenotypes that include mental retardation, autism, and microcephaly. Chromosomal maintenance 1 (CRM1) is a gene commonly missing in patients with 2p15–16.1 microdeletion and one of two genes found in the smallest deletion case. In this study, we investigate the role and mechanism of Crm1 in the developing mouse brain by inhibiting the protein or knocking down the gene in vivo. Inhibition of Crm1 reduces the proliferation and increases p53-dependent apoptosis of the cortical neural progenitors, thereby impeding the growth of embryonic cerebral cortex. Live imaging of mitosis in ex vivo embryonic brain slices reveals that inhibition of CRM1 arrests the cortical progenitors at metaphase. The arrested cells eventually slip into a pseudo-G1 phase without chromosome segregation. The mitotic slippage cells are marked by persistent expression of the spindle assembly checkpoint (SAC), repressing of which rescues the cells from apoptosis. Our study reveals that activating the SAC and inducing the mitotic slippage may lead to apoptosis of the cortical neural progenitors. The resulting cell death may well contribute to microcephaly associated with microdeletion of chromosome 2p15–16.1 involving CRM1.

Enhanced skeletal muscle arteriolar reactivity to ANG II after recovery from ischemic acute renal failure

2005 ◽  
Vol 289 (6) ◽  
pp. R1770-R1776 ◽  
Author(s):  
David P. Basile ◽  
Deborah L. Donohoe ◽  
Shane A. Phillips ◽  
Jefferson C. Frisbee
Keyword(s):  
Skeletal Muscle ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Pressor Response ◽  
Gracilis Muscle ◽  
Ang Ii ◽  
Sprague Dawley

In addition to the long-term renal complications, previous studies suggested that after acute renal failure (ARF), rats manifest an increased pressor response to an overnight infusion of ANG II. The present study tested whether recovery from ARF results in alterations in sensitivity to the peripheral vasculature. ARF was induced in Sprague-Dawley rats by 45 min of bilateral renal ischemia and reperfusion. Animals were allowed to recover renal structure and function for 5–8 wk, after which the acute pressor responses to ANG II were evaluated either in vivo in in situ skeletal muscle arterioles or in isolated gracilis muscle arteries in vitro. Baseline arterial pressure was not different in ARF rats vs. sham-operated controls, although ARF rats exhibited an enhanced pressor response to bolus ANG II infusion compared with control rats. Steady-state plasma ANG II concentration and plasma renin activity were similar between ARF and control rats. Constrictor reactivity of in situ cremasteric arterioles from ARF rats was enhanced in response to increasing concentrations of ANG II; however, no difference was observed in arteriolar responses to elevated Po2, norepinephrine, acetylcholine, or sodium nitroprusside. Isolated gracilis muscle arteries from ARF rats also showed increased vasoconstriction in response to ANG II but not norepinephrine. In conclusion, recovery from ischemic ARF is not associated with hypertension but is associated with increased arteriolar constrictor reactivity to ANG II. Although the mechanisms of this altered responsiveness are unclear, such changes may relate, in part, to cardiovascular complications in patients with ARF and/or after renal transplant.

Plasma renin system during exercise in normal men

1987 ◽  
Vol 63 (1) ◽  
pp. 188-194 ◽  
Author(s):  
J. Staessen ◽  
R. Fagard ◽  
P. Hespel ◽  
P. Lijnen ◽  
L. Vanhees ◽  
...  
Keyword(s):  
Sodium Intake ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Peak Exercise ◽  
Ang Ii ◽  
Similar Extent ◽  
Bicycle Ergometry ◽  
Arterial Blood ◽  
Intensity Of Exercise ◽  
Normal Men

The exercise-related increase in plasma renin activity (PRA) and in the plasma concentration of angiotensin II (ANG II) and aldosterone (Aldo) was studied in 43 healthy volunteers whose 24-h urinary sodium excretion (UVNa) ranged from 10 to 250 mmol. Arterial blood samples were obtained at rest and during bicycle ergometry. Compared with rest, PRA, ANG II, and Aldo rose to a similar extent during light and moderate exercise. However, at peak exercise ANG II increased significantly more (P less than 0.001) than PRA and Aldo. Thus, with increasing intensity of exercise, the slope of the linear regression of ANG II on PRA became significantly (P less than 0.001) steeper, whereas at maximal exercise the Aldo response did not follow the acute rise in ANG II. At rest as well as during exercise, Aldo rose with increasing ANG II, but the stimulatory effect of ANG II on Aldo was attenuated with higher sodium intake, as estimated from UVNa. Finally, independent of the level of physical activity, UVNa was negatively correlated with PRA, ANG II, and Aldo.

BIOLOGICAL SIGNIFICANCE OF ACTIVE AND INACTIVE RENIN IN MAN

1980 ◽  
Vol 85 (1) ◽  
pp. 137-143 ◽  
Author(s):  
P. LIJNEN ◽  
A. AMERY ◽  
R. FAGARD ◽  
L. VERSCHUEREN
Keyword(s):  
Plasma Concentrations ◽  
Biological Significance ◽  
Plasma Renin ◽  
Angiotensin I ◽  
Vitro Assay ◽  
Arterial Blood ◽  
Inactive Renin ◽  
Change In Mean

SUMMARY The biological significance of active and inactive renin was investigated by comparison of an in-vitro assay of active, total and inactive plasma renin concentration (PRC), plasma renin activity (PRA) and plasma concentrations of angiotensin I and II with an in-vivo change in mean arterial blood pressure (MAP) produced by antagonism of angiotensin with treatment with saralasin and by blockade of angiotensin-converting enzyme by treatment with captopril. A significant relationship between the changes in MAP during treatment with saralasin and captopril with the pretreatment levels of PRA, active and total PRC and angiotensin II were found; while the pre-existing level of inactive renin was not a predictor for the hypotensive effect of saralasin and captopril. During treatment with saralasin and captopril significant increases in PRA, plasma angiotensin I concentration and total and active PRC were found and no change in inactive PRC was observed.

Sign in / Sign up

Export Citation Format

Share Document