Pulmonary oxygen toxicity in awake dogs: metabolic and physiological effects

1984 ◽  
Vol 57 (5) ◽  
pp. 1480-1488 ◽  
Author(s):  
A. L. Harabin ◽  
L. D. Homer ◽  
M. E. Bradley
Keyword(s):  
Oxygen Toxicity ◽  
Plasma Renin ◽  
Hemodynamic Instability ◽  
Blood Gas ◽  
Metabolic Capacity ◽  
Pulmonary Endothelium ◽  
Physiological Variables ◽  
Terminal Response ◽  
Ace Activity

Because the pulmonary endothelium is sensitive to O2-induced damage, we studied in vivo angiotensin-converting enzyme (ACE) activity in the lungs of 14 catheterized unanesthetized dogs exposed either to air or continuous 100% O2 at 1 ATA. For 5 days, or until the dog died, we measured physiological variables and lung ACE activity. The metabolic data were analyzed with a model that accounted for the effect of changes in cardiac output. Nine dogs breathing O2 lived 88 +/- 21.8 (SD) h and except for blood O2 tensions were indistinguishible from controls until development of a terminal response lasting only a few hours. Hemodynamic instability preceded a precipitous terminal change in blood gas tensions which resulted in impairment of arterial oxygenation, hypercapnia, and acidosis. Plasma renin activity increased. The metabolic capacity of the pulmonary endothelium of O2-exposed animals decreased with time so that after 96 h it was 50% of the control. That of five control animals did not change with time. Thus changes in lung ACE activity preceded alterations in hemodynamics or gas exchange, and the contributions of each are discussed.

STEROID METABOLISM IN THE PERFUSED HUMAN PLACENTA

1978 ◽  
Vol 87 (1) ◽  
pp. 181-191 ◽  
Author(s):  
Alfred S. Wolf ◽  
Klaus A. Musch ◽  
Werner Speidel ◽  
Jürgen R. Strecker ◽  
Christian Lauritzen
Keyword(s):  
Venous Blood ◽  
Placental Lactogen ◽  
Dehydroepiandrosterone Sulphate ◽  
Metabolic Capacity ◽  
Loading Test ◽  
Lower Range ◽  
Group I ◽  
High Concentrations ◽  
Steroid Precursor

ABSTRACT A new model for the perfusion of human term-placentas has been developed for studies on the placental biogenesis of C-18 and C-19 steroids. For viability criteria, the glucose- and oxygen-consumption, regional perfusion control by dye-infusions or scanning after injection of 99Tc-labelled macroparticles, and the histological qualification were chosen. The recycled perfusate was investigated for the steroids oestrone (Oe1), oestradiol-17β (Oe2), oestriol (Oe3), 4-androstene-3,17-dione (A), testosterone (T), and human placental lactogen (HPL) by radioimmunoassay in controls and perfusions with the foetal steroid precursor dehydroepiandrosterone sulphate (DHA-S). In control perfusions, steroid hormones were found in constant ratios (Oe1:Oe2:Oe3:T:A = 30:1.5:100:0.35:1). Following the administration of 10 mg DHA-S for testing the metabolic capacity of the organ, high concentrations of Oe1 (90–720 ng/ml = 250–3970 % as compared to 100% pre-injection values) were found, shortly preceded by a rapid increase of A (66–1000 ng/ml = 100–16 000 %). A typical surge of T (5.3–147 ng/ml = 265–4640 %) preceded the normally slower increment of Oe2 (22–220 ng/ml = 1570–4330 %). The concentrations of Oe3 and HPL remained nearly unchanged. From different steroid patterns after DHA-S-load, two distinct responses of term-placentas could be differentiated: Group I (n=12) showed high concentrations of Oe1 (3200 ± 940 %), a small increase of T (1020 ± 500%), as well as low and delayed values of Oe2 (1660 ± 450%). In Group II (n = 5), values were high for T (3160 ± 1020%) and Oe2 (3300 ± 1110%), whereas Oe1 was found in a lower range (508 ± 302%). In contrast to in vivo findings in maternal venous blood after DHS-S injection to the mother, oestrone was found in perfusions as the main oestrogen fraction from DHA-S. Thus, the analysis of such metabolic differences might be of help in the interpretation of complex results from the DHA-S-loading test.

scholarly journals Flow-dependent regulation of endothelial Tie2 by GATA3 in vivo

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Temitayo O. Idowu ◽  
Valerie Etzrodt ◽  
Thorben Pape ◽  
Joerg Heineke ◽  
Klaus Stahl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Experimental Models ◽  
Common Denominator ◽  
Dependent Manner ◽  
Pulmonary Endothelium ◽  
Delivery Platform ◽  
Transient Overexpression ◽  
Plasmid Delivery

Abstract Background Reduced endothelial Tie2 expression occurs in diverse experimental models of critical illness, and experimental Tie2 suppression is sufficient to increase spontaneous vascular permeability. Looking for a common denominator among different critical illnesses that could drive the same Tie2 suppressive (thereby leak inducing) phenotype, we identified “circulatory shock” as a shared feature and postulated a flow-dependency of Tie2 gene expression in a GATA3 dependent manner. Here, we analyzed if this mechanism of flow-regulation of gene expression exists in vivo in the absence of inflammation. Results To experimentally mimic a shock-like situation, we developed a murine model of clonidine-induced hypotension by targeting a reduced mean arterial pressure (MAP) of approximately 50% over 4 h. We found that hypotension-induced reduction of flow in the absence of confounding disease factors (i.e., inflammation, injury, among others) is sufficient to suppress GATA3 and Tie2 transcription. Conditional endothelial-specific GATA3 knockdown (B6-Gata3tm1-Jfz VE-Cadherin(PAC)-cerERT2) led to baseline Tie2 suppression inducing spontaneous vascular leak. On the contrary, the transient overexpression of GATA3 in the pulmonary endothelium (jet-PEI plasmid delivery platform) was sufficient to increase Tie2 at baseline and completely block its hypotension-induced acute drop. On the functional level, the Tie2 protection by GATA3 overexpression abrogated the development of pulmonary capillary leakage. Conclusions The data suggest that the GATA3–Tie2 signaling pathway might play a pivotal role in controlling vascular barrier function and that it is affected in diverse critical illnesses with shock as a consequence of a flow-regulated gene response. Targeting this novel mechanism might offer therapeutic opportunities to treat vascular leakage of diverse etiologies.

The Role of Opioid Peptides in the Hormonal Responses to Acute Exercise in Man

1984 ◽  
Vol 67 (5) ◽  
pp. 483-491 ◽  
Author(s):  
A. Grossman ◽  
P. Bouloux ◽  
P. Price ◽  
P. L. Drury ◽  
K. S. L. Lam ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Plasma Renin Activity ◽  
Acute Exercise ◽  
Plasma Renin ◽  
Endogenous Opioids ◽  
Renin Activity ◽  
High Dose ◽  
Hormonal Responses ◽  
Physiological Variables ◽  
Severe Exercise

1. Opioid involvement in the physiological and hormonal responses to acute exercise was investigated in six normal male subjects. Each was exercised to 40% (mild exercise) and 80% (severe exercise) of his previously determined maximal oxygen consumption on two occasions, with and without an infusion of high-dose naloxone. The exercise task was a bicycle ergometer; mild and severe exercise were performed for 20 min each, followed by a recovery period. 2. Exercise produced the expected increases in heart rate, blood pressure, ventilation, tidal volume, respiratory rate, oxygen consumption and carbon dioxide production. After severe exercise, naloxone infusion increased ventilation from 94.8 ± 4.9 litres/min to 105.7 ± 5.0 litres/min (P<0.05), but had no effect on any of the other physiological variables. 3. Exercise-induced changes in several hormones and metabolites were noted, including elevations in circulating lactate, growth hormone (GH), prolactin, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenaline, noradrenaline, plasma renin activity (PRA) and aldosterone. There was no change in plasma met-enkephalin. Naloxone infusion produced the expected increases in LH and cortisol, but also significantly enhanced the elevations in prolactin, adrenaline, noradrenaline, plasma renin activity and aldosterone (P<0.05). 4. Psychological questionnaires revealed minor mood changes after exercise, but no evidence was found for the suggested ‘high’ or euphoria of exercise. Effort was perceived as greater during the naloxone infusion than the saline infusion in every subject. 5. We conclude that endogenous opioids may be important in the control of ventilation and the perception of effort at high levels of power output, and may modulate the responses of circulating catecholamines and the renin-aldosterone system to acute physical stress.

EXTRAHEPATIC AND EXTRARENAL RENIN INACTIVATION IN THE DOG

1974 ◽  
Vol 60 (2) ◽  
pp. 217-222
Author(s):  
R. FAGARD ◽  
E. FOSSION ◽  
M. CAMPFORTS ◽  
A. AMERY
Keyword(s):  
Blood Vessels ◽  
Pulmonary Circulation ◽  
Plasma Renin ◽  
Glass Container ◽  
Plasma Renin Concentration ◽  
Vascular Beds ◽  
Extrarenal Renin

SUMMARY It was demonstrated previously that renin disappears quickly from the circulation after nephrectomy in the hepatectomized dog. In the present study the plasma renin concentration (PRC) was measured in the efferent and afferent blood vessels of several vascular beds (pulmonary circulation, splanchnic region, spleen, both inferior limbs and pelvis, head) in the anhepatic and in the anhepatic and anephric dog in order to investigate extrarenal and extrahepatic renin inactivation. However, no significant arteriovenous differences in PRC could be traced. The blood of these dogs kept in vitro at 37 °C in a glass container showed no decline in PRC within 3 h of removal. Therefore no specific extrahepatic and extrarenal renin-inactivating mechanism was found which could explain the rapid disappearance of renin from the blood in vivo in the anhepatic and anephric dog.

Anti-Hypertensive Effect of Water Extract of Danshen on Renovascular Hypertension Through Inhibition of the Renin Angiotensin System

2002 ◽  
Vol 30 (01) ◽  
pp. 87-93 ◽  
Author(s):  
Dae Gill Kang ◽  
Yong Gab Yun ◽  
Jang Hyun Ryoo ◽  
Ho Sub Lee
Keyword(s):  
Plasma Concentration ◽  
Water Extract ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ace Activity ◽  
Dose Dependent

A study was designed to elucidate the mechanism of anti-hypertensive effects of Danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of Danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of Danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of Danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed. The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of Danshen extract for three weeks. These results suggest that Danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.

Immunotargeting of catalase to lung endothelium via anti-angiotensin-converting enzyme antibodies attenuates ischemia-reperfusion injury of the lung in vivo

2007 ◽  
Vol 293 (1) ◽  
pp. L162-L169 ◽  
Author(s):  
Kai Nowak ◽  
Sandra Weih ◽  
Roman Metzger ◽  
Ronald F. Albrecht ◽  
Stefan Post ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Dry Weight ◽  
Serum Levels ◽  
Converting Enzyme ◽  
Pulmonary Endothelium ◽  
Preferential Expression

Limitation of reactive oxygen species-mediated ischemia-reperfusion (I/R) injury of the lung by vascular immunotargeting of antioxidative enzymes has the potential to become a promising modality for extension of the viability of banked transplantation tissue. The preferential expression of angiotensin-converting enzyme (ACE) in pulmonary capillaries makes it an ideal target for therapy directed toward the pulmonary endothelium. Conjugates of ACE monoclonal antibody (MAb) 9B9 with catalase (9B9-CAT) have been evaluated in vivo for limitation of lung I/R injury in rats. Ischemia of the right lung was induced for 60 min followed by 120 min of reperfusion. Sham-operated animals (sham, n = 6) were compared with ischemia-reperfused untreated animals (I/R, n = 6), I/R animals treated with biotinylated catalase (CAT, n = 6), and I/R rats treated with the conjugates (9B9-CAT, n = 6). The 9B9-CAT accumulation in the pulmonary endothelium of injured lungs was elucidated immunohistochemically. Arterial oxygenation during reperfusion was significantly higher in 9B9-CAT (221 ± 36 mmHg) and sham (215 ± 16 mmHg; P < 0.001 for both) compared with I/R (110 ± 10 mmHg) and CAT (114 ± 30 mmHg). Wet-dry weight ratio of I/R (6.78 ± 0.94%) and CAT (6.54 ± 0.87%) was significantly higher than of sham (4.85 ± 0.29%; P < 0.05), which did not differ from 9B9-CAT (5.58 ± 0.80%). The significantly lower degree of lung injury in 9B9-CAT-treated animals compared with I/R rats was also shown by decreased serum levels of endothelin-1 (sham, 18 ± 9 fmol/mg; I/R, 42 ± 12 fmol/mg; CAT, 36 ± 11 fmol/mg; 9B9-CAT, 26 ± 9 fmol/mg; P < 0.01) and mRNA for inducible nitric oxide synthase (iNOS) [iNOS-GAPDH ratio: sham, 0.15 ± 0.06 arbitrary units (a.u.); I/R, 0.33 ± 0.08 a.u.; CAT, 0.26 ± 0.05 a.u.; 9B9-CAT, 0.14 ± 0.04 a.u.; P < 0.001]. These results validate immunotargeting by anti-ACE conjugates as a prospective and specific strategy to augment antioxidative defenses of the pulmonary endothelium in vivo.

scholarly journals Lophiosilurus alexandri, a sedentary bottom fish, adjusts its physiological parameters to survive to hypoxia condition.

2021 ◽  
Author(s):  
Livia de Assis Porto ◽  
Rafael Magno Costa Melo ◽  
Suzane Lilian Beier ◽  
Ronald Kennedy Luz ◽  
Gisele Cristina Favero
Keyword(s):  
Chloride Cells ◽  
Blood Capillary ◽  
Blood Gas ◽  
Hypoxia Exposure ◽  
Physiological Variables ◽  
Significant Difference ◽  
Undifferentiated Cells ◽  
Morphology And Morphometry ◽  
Hematological And Biochemical Parameters ◽  
Mucus Cells

Abstract We investigated blood gas, hematological and biochemical parameters and gill morphology and morphometry of Lophiosilurus alexandri juveniles submitted to hypoxia for 48 hours followed by recovery for 48 hours. A total of 48 juveniles (360.0 ± 141.6 g) were distributed among eight tanks (120 L) and subjected to hypoxia condition (water with dissolved oxygen at 2.12 ± 0.90 mg L− 1) or normoxia (at 5.60 ± 0.31 mg L− 1). Blood gas values (pH, PvCO2, PvO2, sO2, HCO3−, stHCO3− and base excess) in hypoxia were significantly different from normoxia, while lactate and the electrolytes (K+, Na+, Cl−, Ca2+ and HCO3−) there was no significant change among treatments. The erythrocytes differed significantly between hypoxia and normoxia at 24 h of recovery, while for hemoglobin and hematocrit there were no significant differences. There was a significant difference in glucose, triglycerides, and cholesterol for both normoxia and hypoxia, while plasma protein remained unchanged. All gill components (epithelial cells, erythrocytes, pillar cells, mucus cells, chloride cells, undifferentiated cells, and blood capillary lumen) differed significantly between hypoxia and normoxia. A reduction in the length of the primary lamella was observed in the hypoxia and recovery treatments, when compared to normoxia. The secondary branchial lamella showed no significant difference for both treatments. In general, juveniles of L. alexandri adapted well to hypoxia exposure for 48 h, as they were able to adjust most of their physiological variables to survive this stress condition and return to normoxia within 48 h.

scholarly journals Is the resting rate of oxygen consumption of locomotor muscles in crustaceans limited by the low blood oxygenation strategy?

2001 ◽  
Vol 204 (5) ◽  
pp. 933-940 ◽  
Author(s):  
J. Forgue ◽  
A. Legeay ◽  
J.C. Massabuau
Keyword(s):  
Blood Oxygenation ◽  
Whole Body ◽  
Blood Gas ◽  
Astacus Leptodactylus ◽  
Night Time ◽  
Arterial Blood ◽  
Rate Of Oxygen Consumption ◽  
Locomotor Muscles

Numerous water-breathers exhibit a gas-exchange regulation strategy that maintains O(2) partial pressure, P(O2), in the arterial blood within the range 1–3 kPa at rest during the daytime. In a night-active crustacean, we examined whether this could limit the rate of O(2)consumption (M(O2)) of locomotor muscles and/or the whole body as part of a coordinated response to energy conservation. In the crayfish Astacus leptodactylus, we compared the in vitro relationship between the M(O2) of locomotor muscles as a function of the extracellular P(O2) and P(CO2) and in vivo circadian changes in blood gas tensions at various values of water P(O2). In vitro, the M(O2) of locomotor muscle, either at rest or when stimulated with CCCP, was O(2)-dependent up to an extracellular P(O2) of 8–10 kPa. In vivo, the existence of a night-time increase in arterial P(O2) of up to 4 kPa at water P(O2) values of 20 and 40 kPa was demonstrated, but an experimental increase in arterial P(O2) during the day did not lead to any rise in whole-body M(O2). This suggested that the low blood P(O2) in normoxia has no global limiting effect on daytime whole-body M(O2). The participation of blood O(2) status in shaping the circadian behaviour of crayfish is discussed.

scholarly journals Induction of Apoptosis of Metastatic Mammary Carcinoma Cells In Vivo by Disruption of Tumor Cell Surface CD44 Function

1997 ◽  
Vol 186 (12) ◽  
pp. 1985-1996 ◽  
Author(s):  
Qin Yu ◽  
Bryan P. Toole ◽  
Ivan Stamenkovic
Keyword(s):  
Cell Surface ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Lung Tissue ◽  
Mammary Carcinoma ◽  
Cell Types ◽  
Pulmonary Endothelium ◽  
Soluble Cd44

To understand how the hyaluronan receptor CD44 regulates tumor metastasis, the murine mammary carcinoma TA3/St, which constitutively expresses cell surface CD44, was transfected with cDNAs encoding soluble isoforms of CD44 and the transfectants (TA3sCD44) were compared with parental cells (transfected with expression vector only) for growth in vivo and in vitro. Local release of soluble CD44 by the transfectants inhibited the ability of endogenous cell surface CD44 to bind and internalize hyaluronan and to mediate TA3 cell invasion of hyaluronan-producing cell monolayers. Mice intravenously injected with parental TA3/St cells developed massive pulmonary metastases within 21–28 d, whereas animals injected with TA3sCD44 cells developed few or no tumors. Tracing of labeled parental and transfectant tumor cells revealed that both cell types initially adhered to pulmonary endothelium and penetrated the interstitial stroma. However, although parental cells were dividing and forming clusters within lung tissue 48 h following injection, &gt;80% of TA3sCD44 cells underwent apoptosis. Although sCD44 transfectants displayed a marked reduction in their ability to internalize and degrade hyaluronan, they elicited abundant local hyaluronan production within invaded lung tissue, comparable to that induced by parental cells. These observations provide direct evidence that cell surface CD44 function promotes tumor cell survival in invaded tissue and that its suppression can induce apoptosis of the invading tumor cells, possibly as a result of impairing their ability to penetrate the host tissue hyaluronan barrier.

scholarly journals Identification and biological activity of ovine and caprine calcitonin receptor-stimulating peptides 1 and 2

2008 ◽  
Vol 198 (2) ◽  
pp. 429-437 ◽  
Author(s):  
Christopher J Charles ◽  
Takeshi Katafuchi ◽  
Timothy G Yandle ◽  
Naoto Minamino
Keyword(s):  
Plasma Renin ◽  
New Members ◽  
Amino Terminal ◽  
Peptide Family ◽  
Plasma Camp ◽  
Receptor Activity Modifying Proteins ◽  
Conscious Sheep ◽  
Dose Dependent

We have recently reported the isolation of three new members of the calcitonin (CT) gene-related peptide family of peptides, the CT receptor (CT-R)-stimulating peptides (CRSPs). We now report the sequencing and characterization of ovine/caprine CRSP-1 and caprine CRSP-2. Mature ovine and caprine CRSP-1 are identical and have strong structural homology to CRSP-1s identified to date from other species. As with other CRSP-1s, ovine/caprine CRSP-1 binds to and activates the CT-R but not the CT-like receptor (CL-R) in combination with the receptor activity-modifying proteins (RAMPs). By contrast, caprine CRSP-2 does not activate any of these receptor-RAMP complexes. Intravenous infusions of ovine CRSP-1 to normal conscious sheep induced dose-dependent reduction in plasma total Ca levels (P=0.02) and corrected Ca levels (P=0.017) associated with increases in plasma cAMP (P=0.002). CRSP-1 reduced both plasma amino-terminal pro-C-type natriuretic peptide levels (P=0.006) and plasma renin activity (P=0.028). There were no significant effects observed on hemodynamic or renal indices measured. In conclusion, we have sequenced ovine/caprine CRSP-1 and caprine CRSP-2 precursors. This newly identified CRSP-1 has been shown to share the structural and biological features of CRSP-1s known to date. In vivo studies confirm that ovine CRSP-1 reduces plasma Ca levels in sheep, presumably via a cAMP-mediated mechanism. By contrast, caprine CRSP-2 did not stimulate any combination of CT-R, CL-R, and RAMPs. Accession numbers of cDNA determined in this study are caprine CRSP-1, AB364646; caprine CRSP-2, AB364647; and ovine CRSP-1, AB364648.

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