Production of the Generalized Shwartzman Reaction by Activated Hageman Factor and α-Adrenergic Stimulation

1971 ◽  
Vol 26 (01) ◽  
pp. 071-076 ◽  
Author(s):  
D.G McKay ◽  
J.-G Latour ◽  
Anatalia M. Lopez
Keyword(s):  
Adrenergic Receptor ◽  
Adrenergic Stimulation ◽  
Platelet Phospholipid ◽  
Pregnant Rats ◽  
Hageman Factor ◽  
Glomerular Capillary ◽  
Receptor Sites ◽  
Shwartzman Reaction ◽  
Stimulation Of

SummaryInfusion of activated purified Hageman factor and norepinephrine into pregnant rats produces renal glomerular capillary thrombosis identical to the generalized Shwartzman reaction. Activated Hageman factor alone, norepinephrine alone, and inosithin (a substitute for platelet phospholipid) alone, in addition to the combination of inosithin and norepinephrine were incapable of causing the reaction. These studies confirm the evidence that four basic components of the reaction are 1. activation of Hageman factor, 2. platelet phospholipid, 3. ‘‘fibrinolysin inhibition’’, and 4. stimulation of α-adrenergic receptor sites.

Activation of Hageman Factor by α-Adrenergic Stimulation

1970 ◽  
Vol 23 (03) ◽  
pp. 417-422 ◽  
Author(s):  
D. G McKay ◽  
J.-G Latour ◽  
Mary H. Parrish
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Adrenergic Receptor ◽  
Adrenergic Stimulation ◽  
Hageman Factor ◽  
Intravascular Coagulation ◽  
Receptor Sites ◽  
High Doses ◽  
Stimulation Of

SummaryThe infusion of epinephrine in high doses produces disseminated intravascular coagulation by activation of Hageman factor. The effect is blocked by phenoxybenz-amine and is therefore due to stimulation of α-adrenergic receptor sites.

Adrenergic stimulation of inositol phosphate accumulation in tracheal epithelium

1989 ◽  
Vol 66 (1) ◽  
pp. 504-508 ◽  
Author(s):  
T. Bainbridge ◽  
R. D. Feldman ◽  
M. J. Welsh
Keyword(s):  
Adrenergic Receptor ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messengers ◽  
Receptor Activation ◽  
Adrenergic Stimulation ◽  
Cl Secretion ◽  
Phosphate Accumulation ◽  
Inositol Phosphate Accumulation ◽  
Stimulation Of

To determine whether inositol phosphates are important second messengers in the regulation of Cl- secretion by airway epithelia, we examined the relationship between inositol phosphate accumulation and Cl- secretion in response to adrenergic agonists. We found that epinephrine stimulated Cl- secretion and inositol phosphate accumulation with similar concentration dependence. Although isoproterenol stimulated Cl- secretion, there was no effect of beta-adrenergic receptor activation on inositol phosphate accumulation. In contrast, alpha 1-adrenergic receptor activation stimulated inositol phosphate accumulation but failed to induce Cl- secretion. Another Cl- secretagogue, prostaglandin E1, also failed to stimulate inositol phosphate accumulation. These data suggest that inositol phosphate accumulation is neither sufficient nor required for stimulation of Cl- secretion in cultured canine tracheal epithelial cells.

Response to cardiac sympathetic activation in transgenic mice overexpressing beta 2-adrenergic receptor

1996 ◽  
Vol 271 (2) ◽  
pp. H630-H636 ◽  
Author(s):  
X. J. Du ◽  
E. Vincan ◽  
D. M. Woodcock ◽  
C. A. Milano ◽  
A. M. Dart ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Nerve Stimulation ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Adrenergic Stimulation ◽  
Adrenergic Activity ◽  
Beta 2 ◽  
Stimulation Of

Transgenic mice have been created with 200-fold overexpression of beta 2-adrenergic receptors specifically in the heart. Cardiac function was studied in these transgenic mice and their controls at baseline and during isoproterenol perfusion or sympathetic nerve stimulation. The model used was an in situ buffer-perfused, innervated heart, and the left ventricle maximal derivative of pressure over time (dP/dtmax) and heart rate (HR) were measured. Basal HR and dP/dtmax were 30-40% higher in hearts from transgenic mice than controls. Electrical stimulation of sympathetic nerves (2, 4, and 8 Hz) or infusion of isoproterenol markedly increased HR and dP/dtmax in control hearts. Hearts from transgenic mice did not respond to isoproterenol. However, hearts from transgenic mice retained the HR response to nerve stimulation, and a small increase in dP/dtmax was also detected. Atenolol inhibited the response to nerve stimulation in control hearts but not that in hearts from transgenic mice. ICI-118551 inhibited the response in transgenic hearts. Basal HR and dP/dtmax were decreased by ICI-118551 only in transgenic hearts. Thus overexpression of cardiac beta 2-receptors modifies beta-adrenergic activity, but the responses to endogenous and exogenous adrenergic stimulation are affected differently.

scholarly journals Prevention of the Generalized Shwartzman Reaction by Bradykinin and Prostaglandins

1977 ◽  
Author(s):  
J.G. Latour ◽  
C. Léger-Gauthier ◽  
C. Groulx
Keyword(s):  
Single Injection ◽  
The Other ◽  
Male Rat ◽  
Adrenergic Stimulation ◽  
Pregnant Rat ◽  
Hageman Factor ◽  
Slow Infusion ◽  
Shwartzman Reaction ◽  
The Sacrifice ◽  
Glomerular Capillaries

We have investigated, in the pregnant rat, the implications of Hageman factor and prekallikrein activation in the pathogenesis of the generalized Shwartzman reaction (GSR). We have found that unlike the hyperlipemia animal, the pregnant rat, which develops the GSR after a single injection of endotoxin (S. typhosa 0.4 mg) on day 20 of gestation, does not consume prekallikrein. Prekallikrein was estimated by measurement on TAME of the arginine esterase activity generated by kallikrein upon addition of active Hageman factor to the test plasma. Bradykinin triacetate (2 or 4 μg/kg/min.), prostaglandin (PG) E-, (0.3 μg/kg/min.), PGA2 (1.0 μg/kg/min.) or isoproterenol (0.66 μg/kg/min.) when given as a slow infusion over 4 hours, from the time of the endotoxin to the sacrifice of the animals, were found to prevent the GSR. On the other hand, aspirin (150 mg/kg) or propranolol (2 mg/kg) given before endotoxin enhance the incidence or severity of the GSR. Furthermore, aspirin markedly reduces the prevention generated by bradykinin infusion and to a less extent that of isoproterenol. Finally, indomethacin (7 mg/kg) given twice daily for 3 days sensitizes the male rat to the GSR, since a single injection of endotoxin triggers deposition of fibrin in the glomerular capillaries. It is concluded that bradykinin generates the release of PG’s and that together they prevent, like the α-adrenergic and the D-serotoninergic blocking agents and or like a β-adrenergic stimulation, the renal vasomotor reactions found necessary for the GSR. These results support the hypothesis that impairment of kinin generation may possibly account for the sensitization of the pregnant rat to the GSR.

Vessel Wall and Thrombogenesis - Endotoxin

1973 ◽  
Vol 29 (01) ◽  
pp. 011-026 ◽  
Author(s):  
Donald G McKay
Keyword(s):  
Adrenergic Receptor ◽  
Acute Inflammation ◽  
Vascular System ◽  
Disease Process ◽  
Cortical Necrosis ◽  
Receptor Sites ◽  
Shwartzman Reaction ◽  
Antibody Complex ◽  
Antigen Antibody ◽  
Activator System

SummaryThe generalized Shwartzman reaction is a definitive disease process which is the result of two minor episodes of acute inflammation of the circulating blood. The identifying feature of the reaction is thrombosis of the micro circulation, specifically of glomerular capillary thrombosis which persists long enough to cause bilateral renal cortical necrosis. The reaction is the result of an interplay between leukocytes, platelets, complement, the contact system, the extrinsic prothrombin activator system, adrenal glucocorticoids, adrenal catecholamines, alpha - adrenergic receptor sites and the fibrinolytic enzyme system. The reaction occurs only when these systems are affected within narrow quantitative limits. It is a model of the effects of bacterial endotoxin on the blood-vascular system and has important implications for acute inflammatory episodes of the circulating blood induced by other inflammatory agents such as antigen-antibody complex and particulate matter.

Beta-adrenergic-mediated Cl secretion: evidence for additional non-cAMP-dependent pathway of effect

1990 ◽  
Vol 259 (6) ◽  
pp. L426-L431 ◽  
Author(s):  
R. D. Feldman ◽  
A. Brotherton ◽  
M. J. Welsh
Keyword(s):  
Protein Kinase ◽  
Adenylyl Cyclase ◽  
Adrenergic Receptor ◽  
Chloride Secretion ◽  
Intrinsic Sympathomimetic Activity ◽  
Camp Accumulation ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Kinase A ◽  
Stimulation Of

It has been suggested that beta-adrenergic receptor antagonists with intrinsic sympathomimetic activity, like pindolol, are weak partial agonists for beta-adrenergic-stimulated adenylyl cyclase activation. To evaluate this possibility, beta-adrenergic-mediated chloride secretion was studied in tracheal epithelial cells maintained in primary culture. Pindolol caused a dose-dependent increase in chloride secretion with a half-maximal effective concentration of 91 pM to a maximum that was 30 +/- 3% that of isoproterenol. Pindolol-induced chloride secretion was antagonized by the beta-adrenergic antagonist nadolol. However, in contrast to isoproterenol, pindolol did not stimulate adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, adenylyl cyclase activity, or protein kinase A activation. Further studies examined the coupling of beta-adrenergic stimulation of cAMP accumulation to beta-adrenergic stimulation of chloride secretion. Coincubation of cells with the phosphodiesterase inhibitor RA233 increased maximal isoproterenol-stimulated cAMP accumulation eightfold but did not significantly increase the potency or maximal effect of isoproterenol for chloride secretion. It is clear that beta-adrenergic-stimulated elevations in cAMP mediate chloride secretion. These studies also demonstrate that pindolol, a drug with intrinsic sympathomimetic activity, mediates a beta-adrenergic receptor-specific increase in chloride secretion without increasing adenylyl cyclase nor protein kinase A activities. Thus intrinsic sympathomimetic activity may represent a non-cAMP-dependent mechanism of beta-adrenergic effect.

Adrenergic Stimulation of Regional Plasminogen Activator Release in Rabbits

1992 ◽  
Vol 68 (05) ◽  
pp. 545-549 ◽  
Author(s):  
W L Chandler ◽  
S C Loo ◽  
D Mornin
Keyword(s):  
Lower Extremity ◽  
Plasminogen Activator ◽  
Beta Blocker ◽  
Time Course ◽  
Vascular System ◽  
Adrenergic Stimulation ◽  
Epinephrine Administration ◽  
Adrenergic Antagonist ◽  
Vascular Beds ◽  
Stimulation Of

SummaryThe purpose of this study was to determine whether different regions of the rabbit vascular system show variations in the rate of plasminogen activator (PA) secretion. To start, we evaluated the time course, dose response and adrenergic specificity of PA release. Infusion of 1 µg/kg of epinephrine stimulated a 116 ± 60% (SD) increase in PA activity that peaked 30 to 60 s after epinephrine administration. Infusion of 1 µg/kg of norepinephrine, isoproterenol and phenylephrine had no effect on PA activity. Pretreatment with phentolamine, an alpha adrenergic antagonist, blocked the release of PA by epinephrine while pretreatment with the beta blocker propranolol had no effect. This suggests that PA release in the rabbit was mediated by some form of alpha receptor.Significant arterio-venous differences in basal PA activity were found across the pulmonary and splanchnic vascular beds but not the lower extremity/pelvic bed. After stimulation with epinephrine, PA activity increased 46% across the splanchnic bed while no change was seen across the lower extremity/pelvic bed. We conclude that several vascular beds contribute to circulating PA activity in the rabbit, and that these beds secrete PA at different rates under both basal and stimulated conditions.

Consumption of Hageman Factor Activity in the Generalized Shwartzman Reaction Induced by Liquoid

1970 ◽  
Vol 23 (02) ◽  
pp. 386-404 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch
Keyword(s):  
Partial Thromboplastin Time ◽  
Lethal Dose ◽  
Control Group ◽  
Factor V ◽  
Consumption Coagulopathy ◽  
Factor Activity ◽  
Hageman Factor ◽  
Intravascular Coagulation ◽  
Shwartzman Reaction

SummaryThe role of Hageman factor in triggering intravascular coagulation has been studied in rabbits injected intravenously with Liquoid. Besides changes of coagulation parameters characteristic of consumption coagulopathy (e.g. decrease in platelet counts, fibrinogen levels, factor V activity), a pronounced drop in Hageman factor activity was observed after injection of Liquoid. Likewise, the partial thromboplastin time became prolonged.The activation of Hageman factor in vivo could be prevented by intravenous infusion of lysozyme. Twenty min after starting the lysozyme infusion, the partial thromboplastin time became prolonged from a mean of 29 sec to 108 sec. Animals infused with lysozyme and injected with a lethal dose of Liquoid did not develop a consumption coagulopathy. In the same manner, none of 10 animals treated with lysozyme developed the generalized Shwartzman reaction, whereas in the control group 19 out of 20 animals showed fibrin thrombi in the glomerular capillaries.From the present study it may be concluded that the intravascular coagulation process after intravenous injection of Liquoid is triggered by Hageman factor activation.

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