Influence of Angiotensin II, Ouabain and Hydrostatic Pressure on Inulin and Electrolyte Concentration of Fluid Perfusing Pig Carotid Arteries in Vitro

1979 ◽  
Vol 56 (5) ◽  
pp. 445-453 ◽  
Author(s):  
J. K. Healy ◽  
A. J. Elliott ◽  
I. J. Oweczkin
Keyword(s):  
Angiotensin Ii ◽  
Hydrostatic Pressure ◽  
Arterial Pressure ◽  
Carotid Arteries ◽  
Sodium Concentration ◽  
High Dose ◽  
Electrolyte Homeostasis ◽  
Arterial Contraction ◽  
High Doses

1. Angiotensin II was infused into isolated, perfused pig carotid arteries. The perfusate leaving the arteries was sampled into an Auto-analyzer system which continuously monitored its composition. Arterial pressure was recorded. 2. Low, subpressor doses of angiotensin II raised the perfusate potassium concentration, whereas high doses, which produced contraction, lowered perfusate potassium and sodium concentrations. Inulin and chloride concentrations did not change. 3. The elevation of perfusate potassium with low angiotensin II dosage was appreciable compared with that caused by high doses of ouabain. 4. Neurotransmitter blockade did not alter the low- and high-dose angiotensin II effects. In other sequential dose studies, valine5-angiotensin II and isoleucine5-angiotensin II did not differ in their effects on perfusate composition or arterial contraction. 5. Mechanically increased hydrostatic pressure lowered perfusate sodium concentration, so that increased arterial pressure might have contributed to this aspect of high-dose angiotensin II effects. 6. These effects of angiotensin II might have physiological significance in relation to arterial smooth muscle and to electrolyte homeostasis.

Effect of arterial pressure on drinking and urinary responses to angiotensin II

1988 ◽  
Vol 254 (1) ◽  
pp. R69-R74 ◽  
Author(s):  
M. D. Evered ◽  
M. M. Robinson ◽  
P. A. Rose
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Water Intake ◽  
Fluid Loss ◽  
High Dose ◽  
Ang Ii ◽  
Intravenous Injections ◽  
Drinking Response ◽  
High Doses ◽  
The Relationship

To investigate the relationship between angiotensin II (ANG II) and mean arterial pressure (MAP) in the control of drinking in rats, we infused ANG II intravenously at constant rates (either 50 or 100 ng.kg-1.min-1 for 90 min) and varied MAP by intravenous injections of diazoxide (5-20 mg/kg). Rats were pretreated with captopril to block the endogenous synthesis of ANG II. When given alone, low and high doses of ANG II increased MAP approximately 30 and 50 mmHg, respectively. The low but not the high dose significantly increased water intake above control levels. Both doses caused such a large diuresis and natriuresis that the net effect was fluid loss. Reducing MAP toward normal greatly increased the drinking response to the high but not the low dose of ANG II and reduced the urinary solute and water loss to both doses. These results support the hypothesis that water intake and net fluid gain are inhibited when MAP is above normal. When MAP was reduced below normal in rats given constant infusions of ANG II the amount of water drunk and net fluid gain was proportional to the dose of ANG II but not the dose of diazoxide, the degree of hypotension, or urinary losses. This is consistent with previous reports that ANG II is essential for the drinking response to hypotension. Furthermore, it demonstrates that ANG II is not merely permissive but probably the signal controlling water intake when arterial pressure is reduced below normal.

scholarly journals Toll-Like Receptor Signaling in Airborne Burkholderia thailandensis Infection

2009 ◽  
Vol 77 (12) ◽  
pp. 5612-5622 ◽  
Author(s):  
T. Eoin West ◽  
Thomas R. Hawn ◽  
Shawn J. Skerrett
Keyword(s):  
Low Dose ◽  
Inflammatory Responses ◽  
High Dose ◽  
Tlr Signaling ◽  
Necrosis Factor Alpha ◽  
Airborne Infection ◽  
Essential Components ◽  
High Doses

ABSTRACT Melioidosis is a tropical disease endemic in southeast Asia and northern Australia caused by the gram-negative soil saprophyte Burkholderia pseudomallei. Although infection is often systemic, the lung is frequently involved. B. thailandensis is a closely related organism that at high doses causes lethal pneumonia in mice. We examined the role of Toll-like receptors (TLRs), essential components of innate immunity, in vitro and in vivo during murine B. thailandensis pneumonia. TLR2, TLR4, and TLR5 mediate NF-κB activation by B. thailandensis in transfected HEK293 or CHO cells. In macrophages, TLR4 and the adaptor molecule MyD88, but not TLR2 or TLR5, are required for tumor necrosis factor alpha production induced by B. thailandensis. In low-dose airborne infection, TLR4 is needed for early, but not late, bacterial containment, and MyD88 is essential for control of infection and host survival. TLR2 and TLR5 are not necessary to contain low-dose infection. In high-dose airborne infection, TLR2 deficiency confers a slight survival advantage. Lung and systemic inflammatory responses are induced by low-dose inhaled B. thailandensis independently of individual TLRs or MyD88. These findings suggest that redundancy in TLR signaling or other MyD88-dependent pathways may be important in pneumonic B. thailandensis infection but that MyD88-independent mechanisms of inflammation are also activated. TLR signaling in B. thailandensis infection is substantially comparable to signaling induced by virulent B. pseudomallei. These studies provide additional insights into the host-pathogen interaction in pneumonic Burkholderia infection.

Effect of baroreceptor denervation on stimulation of drinking by angiotensin II in conscious dogs

1991 ◽  
Vol 260 (3) ◽  
pp. E333-E337 ◽  
Author(s):  
C. K. Klingbeil ◽  
V. L. Brooks ◽  
E. W. Quillen ◽  
I. A. Reid
Keyword(s):  
Blood Pressure ◽  
Drinking Water ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Carotid Sinus ◽  
Plasma Osmolality ◽  
Plasma Angiotensin ◽  
High Doses ◽  
Stimulation Of

Angiotensin II causes marked stimulation of drinking when it is injected centrally but is a relatively weak dipsogen when administered intravenously. However, it has been proposed that the dipsogenic action of systemically administered angiotensin II may be counteracted by the pressor action of the peptide. To test this hypothesis, the dipsogenic action of angiotensin II was investigated in dogs, in which low and high baroreceptor influences had been eliminated by denervation of the carotid sinus, aortic arch, and heart. In five sham-operated dogs, infusion of angiotensin II at 10 and 20 ng.kg-1.min-1 increased plasma angiotensin II concentration to 109.2 +/- 6.9 and 219.2 +/- 38.5 pg/ml and mean arterial pressure by 20 and 29 mmHg, respectively, but did not induce drinking. In four baroreceptor-denervated dogs, the angiotensin II infusions produced similar increases in plasma angiotensin II concentration and mean arterial pressure but, in contrast to the results in the sham-operated dogs, produced a dose-related stimulation of drinking. Water intake with the low and high doses of angiotensin II was 111 +/- 44 and 255 +/- 36 ml, respectively. The drinking responses to an increase in plasma osmolality produced by infusion of hypertonic sodium chloride were not different in the sham-operated and baroreceptor-denervated dogs. These results demonstrate that baroreceptor denervation increases the dipsogenic potency of intravenous angiotensin II and provides further support for the hypothesis that the dipsogenic action of intravenous angiotensin II is counteracted by the rise in blood pressure.

scholarly journals Fluconazole plus Cyclosporine: a Fungicidal Combination Effective against Experimental Endocarditis Due to Candida albicans

2000 ◽  
Vol 44 (11) ◽  
pp. 2932-2938 ◽  
Author(s):  
O. Marchetti ◽  
J. M. Entenza ◽  
D. Sanglard ◽  
J. Bille ◽  
M. P. Glauser ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Cyclosporine A ◽  
Test Organism ◽  
The Other ◽  
High Dose ◽  
Therapeutic Results ◽  
Fluconazole Therapy ◽  
High Doses

ABSTRACT Recent observations demonstrated that fluconazole plus cyclosporine (Cy) synergistically killed Candida albicans in vitro. This combination was tested in rats with C. albicansexperimental endocarditis. The MICs of fluconazole and Cy for the test organism were 0.25 and >10 mg/liter, respectively. Rats were treated for 5 days with either Cy, amphotericin B, fluconazole, or fluconazole-Cy. Although used at high doses, the peak concentrations of fluconazole in the serum of rats (up to 4.5 mg/liter) were compatible with high-dose fluconazole therapy in humans. On the other hand, Cy concentrations in serum (up to 4.5 mg/liter) were greater than recommended therapeutic levels. Untreated rats demonstrated massive pseudohyphal growth in both the vegetations and the kidneys. However, only the kidneys displayed concomitant polymorphonuclear infiltration. The therapeutic results reflected this dissociation. In the vegetations, only the fungicidal fluconazole-Cy combination significantly decreased fungal densities compared to all groups, including amphotericin B (P < 0.0001). In the kidneys, all regimens except the Cy regimen were effective, but fluconazole-Cy remained superior to amphotericin B and fluconazole alone in sterilizing the organs (P < 0.0001). While the mechanism responsible for the fluconazole-Cy interaction is hypothetical, this observation opens new perspectives for fungicidal combinations between azoles and other drugs.

scholarly journals Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection.

1987 ◽  
Vol 166 (6) ◽  
pp. 1716-1733 ◽  
Author(s):  
J S Weber ◽  
G Jay ◽  
K Tanaka ◽  
S A Rosenberg
Keyword(s):  
T Cells ◽  
Mhc Class I ◽  
Interleukin 2 ◽  
Class I ◽  
High Dose ◽  
Class I Mhc ◽  
High Doses ◽  
I Gene

We have shown that two weakly immunogenic MCA sarcomas developed in our laboratory that are sensitive to high-dose IL-2 immunotherapy express class I MHC in vivo and in vitro. Two nonimmunogenic MCA sarcomas are relatively insensitive to IL-2 therapy and express minimal or no class I MHC molecules in vivo and in vitro. To study the role of MHC in the therapy of tumors with IL-2, a class I-deficient murine melanoma, B16BL6, was transfected with the Kb class I gene. Expression of class I MHC rendered B16BL6 advanced pulmonary macrometastases sensitive to IL-2 immunotherapy. 3-d micrometastases of CL8-2, a class I transfected clone of B16BL6, were significantly more sensitive to IL-2 therapy than a control nontransfected line. Expression of Iak, a class II MHC molecule, had no effect on IL-2 therapy of transfectant pulmonary micrometastases in F1 mice. By using lymphocyte subset depletion with mAbs directed against Lyt-2, therapy of class I transfectant macrometastases with high-dose IL-2 was shown to involve an Lyt-2 cell. In contrast, regression of micrometastases treated with low-dose IL-2 involved Lyt-2+ cells, but regression mediated by high doses of IL-2 did not. We hypothesize that both LAK and Lyt-2+ T cells effect IL-2-mediated elimination of micrometastases, but only Lyt-2+ T cells are involved in macrometastatic regression. Low doses of IL-2 stimulate Lyt-2+ cells to eliminate class I-expressing micrometastases, but high doses of IL-2 can recruit LAK cells to mediate regression of micrometastases independent of class I expression. Only high-dose IL-2, mediating its effect predominantly via Lyt-2+ cells, is capable of impacting on MHC class I-expressing macrometastases. Macrometastases devoid of class I MHC antigens appear to be resistant to IL-2 therapy.

scholarly journals Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Daniel Santos ◽  
Francisco Gonzalez-Perez ◽  
Xavier Navarro ◽  
Jaume del Valle
Keyword(s):  
Neurite Outgrowth ◽  
Functional Recovery ◽  
Neurotrophic Factors ◽  
Collagen Matrix ◽  
High Dose ◽  
Organotypic Cultures ◽  
High Doses ◽  
Dose Dependent

Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were delivered in a collagen matrix within a silicone tube to repair the severed sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed that NGF and NT-3 did not show preferential effect on sensory regeneration whereas BDNF preferentially promoted motor axons regeneration. Therefore, the selective effects of NGF and NT-3 shown in vitro are lost when they are applied in vivo, but a high dose of BDNF is able to selectively enhance motor neuron regeneration both in vitro and in vivo.

scholarly journals High-Dose Intravenous Ribavirin Therapy for Subacute Sclerosing Panencephalitis

2001 ◽  
Vol 45 (3) ◽  
pp. 943-945 ◽  
Author(s):  
Mitsuaki Hosoya ◽  
Shiro Shigeta ◽  
Shuichi Mori ◽  
Akemi Tomoda ◽  
Seiji Shiraishi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Virus Replication ◽  
Subacute Sclerosing Panencephalitis ◽  
Alpha Interferon ◽  
High Dose ◽  
Sspe Virus ◽  
High Doses

ABSTRACT Two patients with subacute sclerosing panencephalitis (SSPE) were treated safely and effectively with high doses of intravenous ribavirin combined with intraventricular alpha interferon. The ribavirin concentrations maintained in the serum and cerebrospinal fluid were higher than those which inhibit SSPE virus replication in vitro and in vivo.

scholarly journals Hormetic effect of amyloid-beta peptide in hippocampal synaptic plasticity and memory

2021 ◽  
Vol 11 (40) ◽  
pp. 156-156
Author(s):  
Daniela Puzzo ◽  
Agostino Palmeri
Keyword(s):  
Synaptic Plasticity ◽  
Amyloid Beta ◽  
Hippocampal Slices ◽  
Reference Memory ◽  
High Dose ◽  
Low Doses ◽  
Hormetic Effect ◽  
Physiologic Function ◽  
High Doses

Background: The term hormesis refers to a biphasic dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition represented by a J-shaped or U-shaped curve, depending on the parameter measured (Calabrese and Baldwin, Hum Exp Toxicol, 2002). Indeed, several, if not all, physiological molecules (i.e. glutamate, glucocorticoids, nitric oxide) are likely to present a hormetic effect, exhibiting opposite effects at high or low concentrations. In the last few years, we have focused on amyloid-beta (A), a peptide widely known because it is produced in high amounts during Alzheimer’s disease (AD). A is considered a toxic fragment causing synaptic dysfunction and memory impairment (Selkoe, Science, 2002). However, the peptide is normally produced in the healthy brain and growing evidences indicate that it might have a physiologic function. Aim: Based on previous results showing that picomolar concentrations of A42 enhance synaptic plasticity and memory (Puzzo et al, J Neurosci, 2008) and that endogenous A is necessary for synaptic plasticity and memory (Puzzo et al, Ann Neurol, 2011), the aim of our study was to demonstrate the hormetic role of A in synaptic plasticity and memory. Methods: We used 3-month old wild type mice to analyze how synaptic plasticity, measured on hippocampal slices in vitro, and spatial reference memory were modified by treatment with different doses of A (from 2 pM to 20 μM). Results: We demonstrated that A has a hormetic effect (Puzzo et al, Neurobiol Aging, 2012) with low-doses (200 pM) stimulating synaptic plasticity and memory and high-doses (≥ 200 nM) inhibiting these processes. Conclusions: Our results suggest that, paradoxically, very low doses of A might serve to enhance memory at appropriate concentrations and conditions. These findings raise several issues when designing effective and safe approaches to AD therapy.

scholarly journals The early luteal phase administration of estrogen and progesterone does not induce premature luteolysis in normo-ovulatory women

2006 ◽  
Vol 155 (2) ◽  
pp. 355-363 ◽  
Author(s):  
Nicole G M Beckers ◽  
Peter Platteau ◽  
Marinus J Eijkemans ◽  
Nicholas S Macklon ◽  
Frank H de Jong ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Luteal Phase ◽  
Controlled Trial ◽  
Normal Weight ◽  
High Dose ◽  
Ovarian Hyperstimulation ◽  
Lh Surge ◽  
High Doses ◽  
Phase Length

Objective: The luteal phase after ovarian hyperstimulation for in vitro fertilization (IVF) is insufficient. Therefore, luteal phase supplementation is routinely applied in IVF. It may be postulated that premature luteolysis after ovarian hyperstimulation is due to supraphysiological steroid levels in the early luteal phase. In the present study, high doses of steroids are administered after the LH surge in normo-ovulatory volunteers in order to investigate whether this intervention gives rise to endocrine changes and a shortening of the luteal phase. Design: Randomized controlled trial. Methods: Forty non-smoking, normal weight women, between 18 and 37 years of age, with a regular menstrual cycle (24–35 days), received either high dosages of estradiol (E2), progesterone (P), E2+P or no medication. Blood sampling was performed every other day from the day of the LH surge until LH+14. Duration of the luteal phase and endocrine profiles were the main study outcomes. Results: Early luteal phase steroid concentrations achieved by exogenous administration were comparable with levels observed following ovarian hyperstimulation for IVF. No difference in the luteal phase length was observed comparing all groups. However, a significant decrease in LH levels could be observed 6 days after the mid-cycle LH surge (P<0.001) in women receiving P, resulting in accelerated decrease of inhibin A production by the corpus luteum (P=0.001). Conclusion: The present intervention of high-dose steroid administration shortly after the LH surge failed to induce a premature luteolysis regularly in cyclic women. It seems that the induced transient suppression in LH allowed for a timely recovery of corpus luteum function. Other additional factors may be held responsible for the distinct reduction in luteal phase length observed after ovarian hyperstimulation for IVF.

scholarly journals C1-esterase inhibitor treatment: preclinical safety aspects on the potential prothrombotic risk

2014 ◽  
Vol 112 (11) ◽  
pp. 960-971 ◽  
Author(s):  
Elmar Raquet ◽  
Marc Nolte ◽  
Frauke May ◽  
Jochen Müller-Cohrs ◽  
Jenny Björkqvist ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Venous Stasis ◽  
High Dose ◽  
In Vivo Models ◽  
C1 Esterase Inhibitor ◽  
Activity Measurements ◽  
High Doses ◽  
Esterase Inhibitor

SummaryHuman plasma-derived C1-esterase inhibitor (C1–INH) is an efficacious and safe treatment for hereditary angioedema. However, thrombotic events in subjects treated with C1–INH at recommended or offlabel, high doses have been reported. In this study, we addressed the potential prothrombotic risk of C1–INH treatment in high doses using a non-clinical rabbit model. Following intravenous infusion of C1–INH to rabbits at doses up to 800 IU/kg, the exposure and the pharmacodynamic efficacy of C1–INH in rabbits were confirmed by activity measurements of C1-esterase, and coagulation factors XIa and XIIa, respectively. Potential prothrombotic effects were assessed following induction of venous and arterial thrombosis using in vivo models of venous and arterial stasis, complemented by various in vitro assays of coagulation markers. Administration of C1–INH at doses up to 800 IU/ kg did not potentiate thrombus formation during venous stasis. In contrast, inhibition of arterial occlusion was observed upon C1–INH administration when compared with isotonic saline treatment, indicating antithrombotic rather than prothrombotic activity of high dose C1–INH treatment in vivo. This was further confirmed in vitro by decreased thrombin generation, increased activated partial thromboplastin time, clotting time and clot formation time, and inhibition of platelet aggregation. No relevant changes in fibrinolysis or in the levels of thrombin-antithrombin complexes, and prothrombin fragment 1+2 were observed upon high dose C1–INH treatment. The data suggest that treatment of healthy rabbits with high doses of C1–INH could potentially inhibit coagulation and thrombus formation rather than induce a prothrombotic risk.

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