Vasopressin-induced pulmonary vasodilation in rats

1989 ◽  
Vol 257 (2) ◽  
pp. H415-H422 ◽  
Author(s):  
B. R. Walker ◽  
J. Haynes ◽  
H. L. Wang ◽  
N. F. Voelkel
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Systemic Resistance ◽  
Constant Infusion ◽  
Bolus Administration ◽  
Pulmonary Hemodynamics ◽  
Pulmonary Vasodilation ◽  
Isolated Lung ◽  
Series Of Experiments

Experiments were performed to determine the pulmonary vascular responses to exogenous or endogenous arginine vasopressin (AVP) in rats. Both in vitro and in vivo approaches were used to examine the direct pulmonary vasoactive properties of AVP and how those properties affect pulmonary hemodynamics in the intact animal. In conscious, unrestrained rats, constant infusion of AVP (4.0 mU.kg-1.min-1 iv) resulted in a fall in mean pulmonary artery pressure (PAP), although systemic pressure was increased. Coincident with the fall in PAP were similar reductions in cardiac output and heart rate. Similarly, bolus administration of AVP reduced PAP, and this effect was augmented during hypoxia. Another series of experiments examined the effect of endogenous AVP released by arterial hypoxemia on pulmonary hemodynamics in conscious rats. Administration of a specific V1-vasopressinergic antagonist had no effect on the PAP response to hypoxia; however, systemic resistance tended to fall following V1-antagonism. To determine the vasoactive properties of AVP independent of these changes in blood flow, a series of experiments were performed on isolated, perfused rat lungs. Injection of 25, 200, or 2,000 mU of AVP into the circulation of the isolated lung was without effect under normoxic conditions. In contrast, 25 mU AVP elicited reproducible pulmonary vasodilation when injected during ongoing hypoxic pulmonary vasoconstriction. This vasodilatory response was unaffected by meclofenamate or by the platelet-activating factor receptor antagonist SRI 63-441, but was blocked by a specific V1-vasopressinergic antagonist. We conclude that although AVP exerts profound systemic vasoconstriction, the pulmonary circulation appears relatively unaffected by exogenous or endogenous AVP in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of embryonic rat eyes in organ culture

Development ◽  
1968 ◽  
Vol 19 (3) ◽  
pp. 407-414
Author(s):  
R. Christy Armstrong ◽  
Joel J. Elias
Keyword(s):  
Organ Culture ◽  
Culture Medium ◽  
Folic Acid Deficiency ◽  
Experimental Conditions ◽  
Acid Deficiency ◽  
Series Of Experiments ◽  
Development In Vitro ◽  
Ocular System

Abnormalities of the ocular system which appear in organ culture in Waymouth's medium with freshly added glutamine (Armstrong & Elias, 1968) resemble those caused by transitory pteryolglutamic acid (PGA or folic acid) deficiency in vivo (Armstrong & Monie, 1966). The configurations of such malformations as lens herniations, retinal diverticula, and rosette-like formations of the retina are remarkably similar in both cases. The experiments reported in this paper were undertaken in an effort to understand the mechanisms involved in the production of similar abnormalities by two very different experimental conditions: the addition of glutamine in vitro and the transitory deficiency of PGA in vivo. One series of experiments involved the effects of manipulation of the PGA and glutamine content of the culture medium on eye development in vitro. Parallel studies on PGA-deficiency in vivo were undertaken in conjunction with organ-culture experiments in order to compare the effects on abnormal eye morphogenesis.

Comparison of the hemodynamic effects of nitric oxide and endothelium-dependent vasodilators in intact lungs

1990 ◽  
Vol 68 (2) ◽  
pp. 735-747 ◽  
Author(s):  
S. L. Archer ◽  
K. Rist ◽  
D. P. Nelson ◽  
E. G. DeMaster ◽  
N. Cowan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Pulmonary Hypertension ◽  
Feedback Inhibition ◽  
Pressor Response ◽  
Pulmonary Vasculature ◽  
Hemodynamic Effects ◽  
Isolated Lung

The effects of endothelium-dependent vasodilation on pulmonary vascular hemodynamics were evaluated in a variety of in vivo and in vitro models to determine 1) the comparability of the hemodynamic effects of acetylcholine (ACh), bradykinin (BK), nitric oxide (NO), and 8-bromo-guanosine 3′,5′-cyclic monophosphate (cGMP), 2) whether methylene blue is a useful inhibitor of endothelium-dependent relaxing factor (EDRF) activity in vivo, and 3) the effect of monocrotaline-induced pulmonary hypertension on the responsiveness of the pulmonary vasculature to ACh. In isolated rat lungs, which were preconstricted with hypoxia, ACh, BK, NO, and 8-bromo-cGMP caused pulmonary vasodilation, which was not inhibited by maximum tolerable doses of methylene blue. Methylene blue did not inhibit EDRF activity in any model, despite causing increased pulmonary vascular tone and responsiveness to various constrictor agents. There were significant differences in the hemodynamic characteristics of ACh, BK, and NO. In the isolated lung, BK and NO caused transient decreases of hypoxic vasoconstriction, whereas ACh caused more prolonged vasodilation. Pretreatment of these lungs with NO did not significantly inhibit ACh-induced vasodilation but caused BK to produce vasoconstriction. Tachyphylaxis, which was agonist specific, developed with repeated administration of ACh or BK but not NO. Tachyphylaxis probably resulted from inhibition of the endothelium-dependent vasodilation pathway proximal to NO synthesis, because it could be overcome by exogenous NO. Pretreatment with 8-bromo-cGMP decreased hypoxic pulmonary vasoconstriction and, even when the hypoxic pressor response had largely recovered, subsequent doses of ACh and NO failed to cause vasodilation, although BK produced vasoconstriction. These findings are compatible with the existence of feedback inhibition of the endothelium-dependent relaxation by elevation of cGMP levels. Responsiveness to ACh was retained in lungs with severe monocrotaline-induced pulmonary hypertension. Many of these findings would not have been predicted based on in vitro studies and illustrate the importance for expanding studies of EDRF to in vivo and ex vivo models.

Effects of natriuretic peptides and nitroprusside on venous function in trout

1997 ◽  
Vol 273 (2) ◽  
pp. R527-R539 ◽  
Author(s):  
K. R. Olson ◽  
D. J. Conklin ◽  
A. P. Farrell ◽  
J. E. Keen ◽  
Y. Takei ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Aortic Pressure ◽  
Systemic Resistance ◽  
Venous Compliance ◽  
Venous Capacitance ◽  
Unstressed Volume ◽  
Ventral Aorta

Active venous regulation of cardiovascular function is well known in mammals but has not been demonstrated in fish. In the present studies, the natriuretic peptides (NP) rat atrial natriuretic peptide (ANP) and trout ventricular natriuretic peptide (VNP), clearance receptor inhibitor SC-46542, and sodium nitroprusside (SNP) were infused into unanesthetized trout fitted with pressure cannulas in the ventral aorta, dorsal aorta, and ductus Cuvier, and a ventral aorta (VA) flow probe was used to measure cardiac output (CO). In another group, in vivo vascular (venous) capacitance curves were obtained during ANP or SNP infusion. The in vitro effects of NP on vessels and the heart were also examined. ANP, VNP, and SC-46542 decreased central venous pressure (PVen), CO, stroke volume (SV), and gill resistance (RG), whereas systemic resistance (RS) and heart rate (HR) increased. Dorsal aortic pressure (PDA) transiently increased and then fell even though RS remained elevated. ANP decreased mean circulatory filling pressure (MCFP), increased vascular compliance at all blood volumes, and increased unstressed volume in hypovolemic fish. ANP had no direct effect on the heart. ANP responses in vivo were not altered in trout made hypotensive by prior treatment with the angiotensin-converting enzyme inhibitor lisinopril. SNP reduced ventral aortic pressure (PVA), PDA, and RS, increased CO and HR, but did not affect PVen, SV, or RG. SNP slightly decreased MCFP but did not affect compliance or unstressed volume. In vitro, large systemic arteries were more responsive than veins to NP, whereas SNP relaxed both. These results show that, in vivo, NP decrease venous compliance, thereby decreasing venous return, CO, and arterial pressure. Conversely, SNP hypotension is due to decreased RS. This is the first evidence for active regulation of venous capacitance in fish, which probably occurs in small veins or venules. The presence of venous baroreceptors is also suggested.

scholarly journals B-1 cell: the precursor of a novel mononuclear phagocyte with immuno-regulatory properties

2009 ◽  
Vol 81 (3) ◽  
pp. 489-496 ◽  
Author(s):  
José Daniel Lopes ◽  
Mario Mariano
Keyword(s):  
Mammalian Cells ◽  
Giant Cells ◽  
Mononuclear Phagocyte ◽  
Different Types ◽  
Series Of Experiments ◽  
B1 Cells ◽  
Regulatory Properties

Characterization of the origin, properties, functions and fate of cells is a fundamental task for the understanding of physiological and pathological phenomena. Despite the bulk of knowledge concerning the diverse characteristics of mammalian cells, some of them, such as B-1 cells, are still poorly understood. Here we report the results obtained in our laboratory on these cells in the last 10 years. After showing that B-1 cells could be cultured and amplified in vitro, a series of experiments were performed with these cells. They showed that B1 cells reside mostly in the peritoneal and pleural cavities, migrate to distant inflammatory foci, coalesce to form giant cells and participate in granuloma formation, both in vitro and in vivo. They are also able to present antigens to immunologically responsive cells and are endowed with regulatory properties. Further, we have also shown that these cells facilitate different types of infection as well as tumor growth and spreading. These data are presently reviewed pointing to a pivotal role that these cells may play in innate and acquired immunity.

SPECT Quantification of [123I]Iomazenil Binding to Benzodiazepine Receptors in Nonhuman Primates: II. Equilibrium Analysis of Constant Infusion Experiments and Correlation with in vitro Parameters

1994 ◽  
Vol 14 (3) ◽  
pp. 453-465 ◽  
Author(s):  
Marc Laruelle ◽  
Anissa Abi-Dargham ◽  
Mohammed S. AI-Tikriti ◽  
Ronald M. Baldwin ◽  
Yolanda Zea-Ponce ◽  
...  
Keyword(s):  
Specific Activity ◽  
Single Photon ◽  
Benzodiazepine Receptors ◽  
Photon Emission ◽  
Benzodiazepine Receptor ◽  
Equilibrium Analysis ◽  
Constant Infusion ◽  
Scatchard Analysis

In vivo benzodiazepine receptor equilibrium dissociation constant, KD, and maximum number of binding sites, Bmax, were measured by single photon emission computerized tomography (SPECT) in three baboons. Animals were injected with a bolus followed by a constant i.v. infusion of the high affinity benzodiazepine ligand [123I]iomazenil. Plasma steady-state concentration and receptor–ligand equilibrium were reached within 2 and 3 h, respectively, and were sustained for the duration (4–9 h) of the experiments (n = 15). At the end of the experiments, a receptor saturating dose of flumazenil (0.2 mg/kg) was injected to measure nondisplaceable activity. Experiments were carried out at various levels of specific activity, and Scatchard analysis was performed for derivation of the KD (0.59 ± 0.09 n M) and Bmax (from 126 n M in the occipital region to 68 n M in the striatum). Two animals were killed and [125I]iomazenil Bmax and KD were measured at 22 and 37°C on occipital homogenate membranes. In vitro values of Bmax (114 ± 33 n M) and 37°C KD (0.66 ± 0.16 n M) were in good agreement with in vivo values measured by SPECT. This study demonstrates that SPECT can be used to quantify central neuroreceptors density and affinity.

scholarly journals Metformin-stimulated AMPK-α1 promotes microvascular repair in acute lung injury

2013 ◽  
Vol 305 (11) ◽  
pp. L844-L855 ◽  
Author(s):  
Ming-Yuan Jian ◽  
Mikhail F. Alexeyev ◽  
Paul E. Wolkowicz ◽  
Jaroslaw W. Zmijewski ◽  
Judy R. Creighton
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Ex Vivo ◽  
Endothelial Permeability ◽  
Beneficial Effects ◽  
Isolated Lung

Acute lung injury secondary to sepsis is a leading cause of mortality in sepsis-related death. Present therapies are not effective in reversing endothelial cell dysfunction, which plays a key role in increased vascular permeability and compromised lung function. AMP-activated protein kinase (AMPK) is a molecular sensor important for detection and mediation of cellular adaptations to vascular disruptive stimuli. In this study, we sought to determine the role of AMPK in resolving increased endothelial permeability in the sepsis-injured lung. AMPK function was determined in vivo using a rat model of endotoxin-induced lung injury, ex vivo using the isolated lung, and in vitro using cultured rat pulmonary microvascular endothelial cells (PMVECs). AMPK stimulation using N1-(α-d-ribofuranosyl)-5-aminoimidizole-4-carboxamide or metformin decreased the LPS-induced increase in permeability, as determined by filtration coefficient ( Kf) measurements, and resolved edema as indicated by decreased wet-to-dry ratios. The role of AMPK in the endothelial response to LPS was determined by shRNA designed to decrease expression of the AMPK-α1 isoform in capillary endothelial cells. Permeability, wounding, and barrier resistance assays using PMVECs identified AMPK-α1 as the molecule responsible for the beneficial effects of AMPK in the lung. Our findings provide novel evidence for AMPK-α1 as a vascular repair mechanism important in the pulmonary response to sepsis and identify a role for metformin treatment in the management of capillary injury.

Reappraisal of H2S/sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling

2008 ◽  
Vol 294 (6) ◽  
pp. R1930-R1937 ◽  
Author(s):  
Nathan L. Whitfield ◽  
Edward L. Kreimier ◽  
Francys C. Verdial ◽  
Nini Skovgaard ◽  
Kenneth R. Olson
Keyword(s):  
Ischemic Preconditioning ◽  
Baseline Level ◽  
Venous Blood ◽  
Sulfide Concentration ◽  
Potential Significance ◽  
Aortic Blood ◽  
Total Sulfide ◽  
Series Of Experiments

Hydrogen sulfide (H2S) is rapidly emerging as a biologically significant signaling molecule. Studies published before 2000 report low or undetectable H2S (usually as total sulfide) levels in blood or plasma, whereas recent work has reported sulfide concentrations between 10 and 300 μM, suggesting it acts as a circulating signal. In the first series of experiments, we used a recently developed polarographic sensor to measure the baseline level of endogenous H2S gas and turnover of exogenous H2S gas in real time in blood from numerous animals, including lamprey, trout, mouse, rat, pig, and cow. We found that, contrary to recent reports, H2S gas was essentially undetectable (<100 nM total sulfide) in all animals. Furthermore, exogenous sulfide was rapidly removed from blood, plasma, or 5% bovine serum albumin in vitro and from intact trout in vivo. To determine if blood H2S could transiently increase, we measured oxygen-dependent H2S production by trout hearts in vitro and in vivo. H2S has been shown to mediate ischemic preconditioning (IPC) in mammals. IPC is present in trout and, unlike mammals, the trout myocardium obtains its oxygen from relatively hypoxic systemic venous blood. In vitro, myocardial H2S production was inversely related to Po2, whereas we failed to detect H2S in ventral aortic blood from either normoxic or hypoxic fish in vivo. These results provide an autocrine or paracrine mechanism for myocardial coupling of hypoxia to H2S in IPC, i.e., oxygen sensing, but they fail to provide any evidence that H2S signaling is mediated by the circulation.

scholarly journals A Pilot Study on Efficacy of Lipid Bubbles for Theranostics in Dogs with Tumors

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2423
Author(s):  
Inoru Yokoe ◽  
Yusuke Murahata ◽  
Kazuki Harada ◽  
Yuji Sunden ◽  
Daiki Omata ◽  
...  
Keyword(s):  
Cervical Region ◽  
Focal Liver Lesions ◽  
Contrast Imaging ◽  
Contrast Enhanced Ultrasonography ◽  
Series Of Experiments ◽  
Diagnostic Applications ◽  
Hepatic Portal ◽  
Large Animals

The combined administration of microbubbles and ultrasound (US) is a promising strategy for theranostics, i.e., a combination of therapeutics and diagnostics. Lipid bubbles (LBs), which are experimental theranostic microbubbles, have demonstrated efficacy in vitro and in vivo for both contrast imaging and drug delivery in combination with US irradiation. To evaluate the clinical efficacy of LBs in combination with US in large animals, we performed a series of experiments, including clinical studies in dogs. First, contrast-enhanced ultrasonography using LBs (LB-CEUS) was performed on the livers of six healthy Beagles. The hepatic portal vein and liver tissue were enhanced; no adverse reactions were observed. Second, LB-CEUS was applied clinically to 21 dogs with focal liver lesions. The sensitivity and specificity were 100.0% and 83.3%, respectively. These results suggested that LB-CEUS could be used safely for diagnosis, with high accuracy. Finally, LBs were administered in combination with therapeutic US to three dogs with an anatomically unresectable solid tumor in the perianal and cervical region to determine the enhancement of the chemotherapeutic effect of liposomal doxorubicin; a notable reduction in tumor volume was observed. These findings indicate that LBs have potential for both therapeutic and diagnostic applications in dogs in combination with US irradiation.

scholarly journals Platelet Alterations Caused by Antiplatelet Antibodies in the Circulation

1977 ◽  
Author(s):  
T. Nagasawa ◽  
B.K. Kim ◽  
M.G. Baldini
Keyword(s):  
Platelet Count ◽  
Specific Activity ◽  
Rabbit Model ◽  
Antiplatelet Antibodies ◽  
Large Numbers ◽  
Severe Reduction ◽  
Series Of Experiments ◽  
Specific Activities

It is known that antiplatelet antibodies cause loss of platelet cytoplasmic and granular contents in vitro. It is, however, unknown whether similar platelet changes occur in vivo, in the circulation, leading to destruction and phagocytosis of platelets in the R.E. system. To study this possibility a rabbit model was devised. Severe and stable thrombocytopenia was first produced in rabbits by one intravenous injection of Adriamycin. Large numbers of allogenic platelets labeled in vitro with 51Cr and 14C-serotonin were then infused to raise the circulating platelet count to 180-250 × 103/mm3. A dilute heteroimmune antiplatelet serum prepared in the guinea pig was infused intravenously and platelet samples were collected four times during the subsequent 30 minutes to 24 hours. Platelet hexokinase and β-glucuronidase, 14C-serotonin and 51Cr were measured. Within the first 60 min the specific activity of 51Cr in platelets decreased by 21%, 14C-serotonin declined by 30%, hexokinase by 5% and β-glucuronidase by 29%. During the subsequent 24 hours only 51Cr and hexokinase registered a mild decrease but 51C-serotonin and β-glucuronidase remained essentially unchanged. In a second series of experiments the effect of platelet alloantibodies was studied in rabbits previously immunized with allogenic platelets. The decline in the specific activities of the enzymes and 14C-serotonin was similar to that observed in animals treated with heteroimmune sera but loss of 51Cr was more severe. These results demonstrate that the platelets remaining in the circulation after the disappearance of the immediate effect of hetero- or alloantibodies were qualitatively altered with a severe reduction of their granular and cytoplasmic contents.

scholarly journals Amphotericin B Penetrates into the Central Nervous System through Focal Disruption of the Blood-Brain Barrier in Experimental Hematogenous Candida Meningoencephalitis

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Jessica M. Valdez ◽  
Vasilios Pyrgos ◽  
Martin J. Lizak ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amphotericin B ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blue Dye ◽  
Bolus Administration ◽  
Blood Brain ◽  
Mri Scans

ABSTRACT Hematogenous Candida meningoencephalitis (HCME) is a life-threatening complication of neonates and immunocompromised children. Amphotericin B (AmB) shows poor permeation and low cerebrospinal fluid (CSF) concentrations but is effective in the treatment of HCME. In order to better understand the mechanism of CNS penetration of AmB, we hypothesized that AmB may achieve focally higher concentrations in infected CNS lesions. An in vitro blood-brain barrier (BBB) model was serially infected with Candida albicans. Liposomal AmB (LAMB) or deoxycholate AmB (DAMB) at 5 μg/ml was then provided, and the vascular and CNS compartments were sampled 4 h later. For in vivo correlation, rabbits with experimental HCME received a single dose of DAMB at 1 mg/kg of body weight or LAMB at 5 mg/kg and were euthanized after 1, 3, 6, and 24 h. Evans blue dye solution (2%, 2 ml/kg) administered intravenously (i.v.) at 1 h prior to euthanasia stained infected regions of tissue but not histologically normal areas. AmB concentrations in stained and unstained tissue regions were measured using ultraperformance liquid chromatography. For selected rabbits, magnetic resonance imaging (MRI) scans performed on days 1 to 7 postinoculation were acquired before and after i.v. bolus administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) at 15-min intervals through 2 h postinjection. The greatest degree of penetration of DAMB and LAMB through the in vitro BBB occurred after 24 h of exposure (P = 0.0022). In vivo the concentrations of LAMB and DAMB in brain abscesses were 4.35 ± 0.59 and 3.14 ± 0.89 times higher, respectively, than those in normal tissue (P ≤ 0.019). MRI scans demonstrated that Gd-DTPA accumulated in infected areas with a disrupted BBB. Localized BBB disruption in HCME allows high concentrations of AmB within infected tissues, despite the presence of low cerebrospinal fluid concentrations.

Sign in / Sign up

Export Citation Format

Share Document