ovalbumin and Hypotension

Anaphylactic shock (AS) is a life-threatening, multisystem disorder arising from sudden release of mast cell- and basophil-derived mediators into the circulation. In this study, we have used a Wistar rat model to investigate AS-associated histopathologic changes in various organs. Rats were sensitized with ovalbumin (1 mg s.c), and AS was induced by intravenous injection of ovalbumin (1 mg). Experimental groups included nonallergic rats (n = 6) and allergic rats (n = 6). Heart rate and blood pressure were monitored during one hour. Organs were harvested at the end of the experiment and prepared for histologic and immunohistochemical studies. Lung, small bowel mucosa and spleen were found to undergo heavy infiltration by mast cells and eosinophils, with less prominent mast cell infiltration of cardiac tissue. The mast cells in lung, small bowel and spleen exhibited increased expression of tryptase, c-kit and induced nitric oxide synthase (iNOS). Increased expression of endothelial nitric oxide synthase (eNOS) by vascular endothelial cells was noted principally in lung, heart and small bowel wall. The Wistar rat model of AS exhibited accumulation of mast cells and eosinophils in the lung, small bowel, and spleen to a greater extent than in the heart. We conclude that lung and gut are principal inflammatory targets in AS, and likely contribute to the severe hypotension of AS. Targeting nitric oxide (NO) production may help reduce AS mortality.

Topics: Anaphylaxis; Animals; Disease Models, Animal; Hypotension; Inflammation; Injections, Intravenous; Injections, Subcutaneous; Male; Nitric Oxide; Ovalbumin; Rats; Rats, Wistar

We determined the renal responses to anaphylaxis and the effects of a nitric oxide synthesis inhibitor, L-NAME, in anesthetized rats and isolated perfused rat kidneys. After the ovalbumin antigen injection, the sensitized rats showed transient and substantial decreases in mean blood pressure and renal blood flow and an increase in renal vascular resistance. Creatinine clearance, a measure of renal function, decreased to 53% baseline at 2 h after antigen. L-NAME pretreatment significantly enhanced the antigen-induced renal vasoconstriction and renal dysfunction. Moreover, plasma creatinine levels significantly increased only in the L-NAME pretreated rats. Separately, in isolated perfused kidneys, we observed the antigen-induced renal vasoconstriction and its augmentation by L-NAME. In conclusion, the renal vascular response to the antigen is vasoconstriction, which is enhanced by L-NAME in both isolated perfused rat kidneys and anesthetized rats; it is accompanied by renal dysfunction, which is also augmented by L-NAME.

Topics: Anaphylaxis; Anesthesia; Animals; Hypotension; Kidney; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Ovalbumin; Rats; Rats, Sprague-Dawley; Vascular Resistance

Anaphylactic shock is life-threatening, but pathophysiology of the stomach lesion remains unclear. We determined gastric hemodynamics and gastric functions during anaphylactic hypotension, as compared to hypotension induced by hemorrhage or sodium nitroprusside (SNP) in anesthetized and ovalbumin-sensitized Sprague-Dawley rats. Systemic arterial pressure, portal venous pressure, and gastric arterial blood flow were measured, and gastric vascular resistance (GVR) was determined. Separately, the intragastric pressure (IGP) and gastric effluent, as a measure of gastric flux, were continuously measured. During anaphylaxis, GVR decreased only transiently at 0.5 min, followed by an increase. IGP increased markedly, while gastric flux decreased. During hemorrhage, GVR and IGP increased, while gastric flux did not change. When SNP was injected, both GVR and IGP decreased and gastric flux increased only just after injection. In conclusion, gastric vasodilatation occurs only transiently after antigen injection, and gastric motility increases, but gastric emptying deceases during anaphylactic hypotension in anesthetized rats.

Topics: Anaphylaxis; Anesthesia; Animals; Arterial Pressure; Gastric Emptying; Gastrointestinal Motility; Hemodynamics; Hemorrhage; Hypotension; Male; Nitroprusside; Ovalbumin; Portal Pressure; Rats; Rats, Sprague-Dawley; Stomach; Vascular Resistance; Vasodilation; Vasodilator Agents

The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall.. To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS.. Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured.. All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L. Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.

Topics: Airway Obstruction; Anaphylaxis; Animals; Arterial Pressure; Bronchial Spasm; Capillary Leak Syndrome; Epinephrine; Hypotension; Neurophysins; Ovalbumin; Protein Precursors; Rats; Respiratory System; Vasopressins

Systemic anaphylaxis is life-threatening, and its pathophysiology is not fully clarified. Mice are frequently used for experimental study on anaphylaxis. However, the hemodynamic features and mechanisms of mouse anaphylactic hypotension remain unknown. Therefore, we determined mechanisms of systemic and pulmonary vascular response to anaphylactic hypotension in anesthetized BALB/c mice by using receptor antagonists of chemical mediators.. Anaphylaxis was actively induced by an intravenous injection of the ovalbumin antigen into open-chest artificially ventilated sensitized mice. Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), left atrial pressure, central venous pressure, and aortic blood flow (ABF) were continuously measured.. In sensitized control mice, MAP and ABF showed initial, transient increases, followed by progressive decreases after the antigen injection. Total peripheral resistance (TPR) did not decrease, while PAP initially and transiently increased to 18.5±0.5mmHg and pulmonary vascular resistance (PVR) also significantly increased. The antigen-induced decreases in MAP and ABF were attenuated by pretreatment with either a platelet-activating factor (PAF) receptor antagonist, CV6209, or a histamine H1 receptor antagonist, diphenhydramine, and were abolished by their combination. Diphenhydramine augmented the initial increases in PAP and PVR, but did not affect the decrease of the corresponding MAP fall. The antagonists of either leukotriene C4 or serotonin, alone or in combination with CV6209, exerted no significant effects.. Mouse anaphylactic hypotension is caused by a decrease in cardiac output but not vasodilatation, via actions of PAF and histamine. The slight increase in PAP is not involved in mouse anaphylactic hypotension.

Topics: Anaphylaxis; Animals; Arterial Pressure; Cardiac Output; Diphenhydramine; Hemodynamics; Histamine; Hypotension; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Platelet Activating Factor; Platelet Membrane Glycoproteins; Pyridinium Compounds; Receptors, G-Protein-Coupled; Vascular Resistance; Vasoconstriction; Vasodilation

Allergens can induce anaphylactic shock and death due to serve hypotension. Potassium channel blockers (K(+)(ATP)) such as glyburide (GLY) induce vasoconstriction. The effect of (K(+)(ATP)) channel blockers on anaphylactic shock is poorly understood. Objective of the study was to test the hypothesis that GLY reduces hypotension induced in anaphylactic shock and increases survival. Rats were grouped into: G1-N=Naïve; G2-SC=Sensitized-Control; G3-SG=Sensitized-GLY (glyburide 40 mg/kg); G4-SE=Sensitized-EPI (epinephrine 10 mg/kg). G2 to G4 groups were sensitized with ovalbumin (OVA) and shock was induced by i.v. injection of OVA. Treatments were administered intravenously 5 min later. Mean arterial pressure (MAP), heart rate (HR), and mean survival time (MST) were measured for 60 min following OVA injection and treatments administration. At the end of the experiment, blood withdrawal was performed to measure plasma levels of histamine, leukotriene B(4) (LTB(4)), prostaglandin E(2) (PGE(2)) and prostaglandin F(2) (PGF(2)). Additionally blood gas (paO2, paCO2, SaO2) and electrolytes (Na(+), K(+) and Ca (++)) were measured. MAP was normal in G1-N; severe hypotension, negative inotropic and short MST were observed in G2-SC; normalization of MAP, with lesser negative inotropism and increased MST were observed in G3-SG; full recovery was observed in G4-SE. Histamine level was significantly higher in G2-SC; reduced in G3-SG and G4-SE. PGE(2) increased in G3-SG; PGF(2) increased in G2-SC and G3-SG. Na(+) and Ca (++) concentration decreased in sensitized rats but reversed in treated groups, without change in K(+) concentration. In conclusion, our data suggest that administration of GLY reduced hypotension and increases survival time in rat anaphylactic shock.

Topics: Allergens; Anaphylaxis; Animals; Arterial Pressure; Dinoprost; Dinoprostone; Glyburide; Heart Rate; Histamine; Hypotension; Leukotriene B4; Male; Ovalbumin; Potassium Channel Blockers; Rats; Rats, Wistar

To determine fluid extravasation in the splanchnic vascular bed during anaphylactic hypotension, the mesenteric lymph flow (Q(lym)) was measured in anesthetized rats sensitized with ovalbumin, along with the systemic arterial pressure (P(sa)) and portal venous pressure (P(pv)). When the antigen was injected into the sensitized rats (n = 10), P(sa) decreased from 125 ± 4 to 37 ± 2 mmHg at 10 min with a gradual recovery, whereas P(pv) increased by 16 mmHg at 2 min and returned to the baseline at 10 min. Q(lym) increased 3.3-fold from the baseline of 0.023 ± 0.002 g/min to the peak levels of 0.075 ± 0.009 g/min at 2 min and returned to the baseline within 12 min. The lymph protein concentrations increased after antigen, a finding indicating increased vascular permeability. To determine the role of the P(pv) increase in the antigen-induced increase in Q(lym), P(pv) of the nonsensitized rats (n = 10) was mechanically elevated in a manner similar to that of the sensitized rats by compressing the portal vein near the hepatic hilus. Unexpectedly, P(pv) elevation alone produced a similar increase in Q(lym), with the peak comparable to that of the sensitized rats. This finding aroused a question why the antigen-induced increase in Q(lym) was limited despite the presence of increased vascular permeability. Thus the changes in splanchnic vascular surface area were assessed by measuring the mesenteric arterial flow. The mesenteric arterial flow was decreased much more in the sensitized rats (75%; n = 5) than the nonsensitized P(pv) elevated rats (50%; n = 5). In conclusion, mesenteric lymph flow increases transiently after antigen presumably due to increased capillary pressure of the splanchnic vascular bed via downstream P(pv) elevation and perfusion and increased vascular permeability in anesthetized rats. However, this increased extravasation is subsequently limited by decreases in vascular surface area and filtration pressure.

Topics: Anaphylaxis; Animals; Antigens; Capillary Permeability; Hypotension; Lymph; Lymphatic Vessels; Male; Mesenteric Arteries; Models, Animal; Ovalbumin; Portal Pressure; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Splanchnic Circulation

The role of the hypovolemic component secondary to the microcirculatory changes in the onset of inaugural anaphylactic hypotension remains debated. We investigated the microcirculatory permeability in a model of anaphylactic shock using a fluorescence confocal microscopy imaging system.. Ovalbumin-sensitized anesthetized Brown Norway rats were randomly allocated into two groups (n = 6/group): control and anaphylaxis, respectively induced by intravenous saline or ovalbumin at time 0 (T0). The mesentery was surgically exposed. Macromolecular fluorescein isothiocyanate-dextran was intravenously injected (T0-5min) allowing in vivo visualization of the mesenteric microvascular network by fluorescence microscopy. After a period of stabilization of the contrast agent concentration, a 5-s movie was recorded to obtain baseline signal intensity. Following T0, 5-s movies were recorded every 30 s for 30 min. Capillary leakage of fluorescein isothiocyanate-dextran was assessed in interstitium and compared between groups. Data are expressed as mean ± SD.. Following anaphylactic shock onset, an early, progressive, and global signal intensity increase over time was detected in the interstitium. Mean index leakage differed between control and anaphylaxis (respectively 20 ± 11 vs. 170 ± 127%; P < 0.0001), starting at 2 min after shock onset and progressively increasing. Index leakage correlated with the drop in arterial blood pressure until T0 + 10 min (r = -0.75, P = 0.0001).. During anaphylaxis, interstitial capillary leakage occurs within minutes after shock onset. Compared with controls, the mesenteric microcirculation showed at least 8-fold-increased macromolecular capillary leakage. The inflammation-induced microcirculatory changes with subsequent intravascular fluid transfer might be involved in the onset of the inaugural hypotension during anaphylactic shock.

Topics: Anaphylaxis; Animals; Capillaries; Capillary Permeability; Hypotension; Male; Ovalbumin; Random Allocation; Rats; Rats, Inbred BN

Anaphylactic shock in rats is characterized by antigen-induced hepatic venoconstriction and the resultant portal hypertension. We determined the role of portal hypertension in anaphylactic hypotension by using the side-to-side portacaval shunt- and sham-operated rats sensitized with ovalbumin (1 mg). We measured the mean arterial blood pressure (MAP), portal venous pressure (PVP), and central venous pressure (CVP) under pentobarbital anesthesia and spontaneous breathing. Anaphylactic hypotension was induced by an intravenous injection of ovalbumin (0.6 mg). In sham rats, the antigen caused not only an increase in PVP from 11.3 cmH(2)O to the peak of 27.9 cmH(2)O but also a decrease in MAP from 103 mmHg to the lowest value of 41 mmHg. CVP also decreased significantly after the antigen. In the portacaval shunt rats, in response to the antigen, PVP increased slightly, but significantly, to the peak of 17.5 cmH(2)O, CVP did not decrease, and MAP decreased to a lesser degree with the lowest value being 60 mmHg. These results suggest that the portacaval shunt attenuated anaphylactic portal hypertension and venous return decrease, partially preventing anaphylactic hypotension. In conclusion, portal hypertension is involved in rat anaphylactic hypotension presumably via splanchnic congestion resulting in decreased venous return and thus systemic arterial hypotension.

Topics: Anaphylaxis; Anesthesia; Animals; Antigens; Blood Pressure; Central Venous Pressure; Hypertension, Portal; Hypotension; Liver; Liver Circulation; Male; Ovalbumin; Portacaval Shunt, Surgical; Portal Pressure; Rats; Rats, Sprague-Dawley; Veins; Venous Pressure

1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis-induced segmental venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the venoconstriction of perfused livers was also examined. 2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague-Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (P(pv)) and sinusoidal pressure were measured to determine the pre- and post-sinusoidal resistances (R(pre) and R(post), respectively). In conscious rats, systemic arterial pressure (SAP) and P(pv) were determined. 3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6- and 1.7-fold increases in R(pre) and R(post), respectively. The anaphylaxis-induced increase in R(pre) was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester (100 micromol/L) 10 min prior to the injection of antigen enhanced anaphylactic venoconstriction, but did not alter the effect of exercise training on the increase in R(pre). In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats. 4. In conclusion, exercise training attenuates the anaphylaxis-induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in conscious rats.

Topics: Anaphylaxis; Animals; Enzyme Inhibitors; Hypotension; Liver; Liver Circulation; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Ovalbumin; Perfusion; Physical Conditioning, Animal; Portal Pressure; Rats; Rats, Sprague-Dawley; Vascular Resistance; Vasoconstriction

Hepatic venoconstriction plays a significant role in anaphylactic hypotension in anesthetized rats. The purpose of this study is to determine whether the primary site of anaphylactic venoconstriction in the liver venous circulation occurs prior to or distal to the sinusoidal capillaries. We also determined whether the hepatic blood volume is increased during anaphylactic hypotension.. We measured, using a servo-null micropipette pressure-measuring system, the hepatic venular transmural pressure (P micro hv) at the liver surface of anesthetized rats sensitized with the antigen of ovalbumin (1 mg). We also measured the liver lobe thickness, using the ultrasonic crystal dimension measuring system. Anaphylactic hypotension was induced by an intravenous injection of 0.6 mg ovalbumin.. When the antigen was injected, the systemic arterial pressure decreased profoundly from 118+/-9 to 45+/-4 mm Hg, which was accompanied by an increase in Ppv and P micro hv: P micro hv only transiently increased from 3.1+/-0.9 to 8.8+/-1.5 cm H(2)O at 1 min and then rapidly returned to the baseline within 2 min, when Ppv continued to increase and reached the peak of 36+/-7 cm H(2)O at 3.5 min after antigen. This greater increase in Ppv-to-P micro hv gradient than that in P micro hv-to-Pcv gradient after antigen indicated that the constriction of the portal veins and the sinusoids much predominates over that of the hepatic veins. Along with this hepatic pre- and sinusoidal constriction, the liver lobe thickness significantly decreased by 4% after antigen.. Pre-sinusoidal constriction during anaphylactic shock in anaesthetized rats increased the portal venous pressure while the hepatic venular pressure only increased slightly and transiently. This predominant pre-sinusoidal constriction is accompanied by a decrease in liver volume.

Topics: Anaphylaxis; Anesthesia; Animals; Antigens; Blood Pressure; Blood Volume; Hepatic Veins; Hypotension; Liver; Liver Circulation; Male; Organ Size; Ovalbumin; Portal Pressure; Portal Vein; Rats; Rats, Sprague-Dawley; Time Factors; Vasoconstriction; Veins; Venous Pressure

We determined the roles of platelet-activating factor (PAF) and histamine in anaphylactic hypotension in ovalbumin-sensitized anesthetized BALB/c mice. The effects of PAF and histamine on hemodynamic variables were studied by measuring the systemic arterial (Psa), portal venous (Ppv) and central venous (Pcv) pressures. Intravenous PAF evoked a biphasic Psa response, an initial rapid and transient drop followed by marked hypotension, accompanied by a decrease in Pcv. Histamine caused only mild systemic hypotension. Both agents similarly increased Ppv by approximately 4 cm H(2)O at high doses. After an injection of antigen, Psa initially increased slightly and then decreased from the baseline of 94 +/- 1 mm Hg to 46 +/- 1 mm Hg at 10 min after antigen administration, with Pcv decreasing by 2.5 cm H(2)O. Ppv increased by 3.5 cm H(2)O at 5 min after antigen injection. Pretreatment with either CV-6209 (PAF receptor antagonist, 1 mg/kg) or diphenhydramine (histamine H(1) receptor antagonist, 20 mg/kg) significantly attenuated an antigen-induced decrease in Psa. The inhibitory action of CV-6209 was greater than that of diphenhydramine, and the combination of these 2 antagonists almost completely inhibited the anaphylactic hypotension. In contrast, the antigen-induced increase in Ppv was attenuated by CV-6209 alone but augmented by diphenhydramine. It is concluded that anaphylactic hypotension is mainly mediated by PAF and, to a lesser extent, by histamine in anesthetized BALB/c mice.

Topics: Anaphylaxis; Animals; Blood Pressure; Diphenhydramine; Histamine; Histamine H1 Antagonists; Hypotension; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Platelet Activating Factor; Platelet Membrane Glycoproteins; Pyridinium Compounds; Receptors, G-Protein-Coupled; Receptors, Histamine H1

We determined the roles of liver and splanchnic vascular bed in anaphylactic hypotension in anesthetized rats and the effects of anaphylaxis on hepatic vascular resistances and liver weight in isolated perfused rat livers. In anesthetized rats sensitized with ovalbumin (1 mg), an intravenous injection of 0.6 mg ovalbumin caused not only a decrease in systemic arterial pressure from 120 +/- 9 to 43 +/- 10 mmHg but also an increase in portal venous pressure that persisted for 20 min after the antigen injection (the portal hypertension phase). The elimination of the splanchnic vascular beds, by the occlusions of the celiac and mesenteric arteries, combined with total hepatectomy attenuated anaphylactic hypotension during the portal hypertension phase. For the isolated perfused rat liver experiment, the livers derived from sensitized rats were hemoperfused via the portal vein at a constant flow. Using the double-occlusion technique to estimate the hepatic sinusoidal pressure, presinusoidal (R(pre)) and postsinusoidal (R(post)) resistances were calculated. An injection of antigen (0.015 mg) caused venoconstriction characterized by an almost selective increase in R(pre) rather than R(post) and liver weight loss. Taken together, these results suggest that liver and splanchnic vascular beds are involved in anaphylactic hypotension presumably because of anaphylactic presinusoidal contraction-induced portal hypertension, which induced splanchnic congestion resulting in a decrease in circulating blood volume and thus systemic arterial hypotension.

Topics: Anaphylaxis; Anesthesia; Animals; Hypertension, Portal; Hypotension; Liver Circulation; Male; Ovalbumin; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Vascular Resistance; Vasoconstriction

Anaphylactic shock accidents after allergen exposure are frequent. After immunization with ovalbumin (OVA), a common dietary constituent, we evaluated the efficacy of pretreatment with histamine-receptor or serotonin-receptor blockers administered alone or in combination with a nitric oxide synthase inhibitor (L-NAME) on OVA-induced anaphylactic shock in Brown Norway rats. Animals were allocated to the following groups (n = 6 each): control (0.9% saline); diphenydramine (15 mg kg(-1)); cimetidine (20 mg kg(-1)); diphenydramine + cimetidine; dihydroergotamine (50 microg kg(-1)); diphenydramine + cimetidine + dihydroergotamine; L-NAME (100 mg/kg) alone or associated with diphenydramine, cimetidine, diphenydramine + cimetidine, dihydroergotamine, or diphenydramine + cimetidine + dihydroergotamine. Mean arterial blood pressure (MABP), heart rate (HR), and survival time were monitored for 60 min following treatment. The shock was initiated with i.v. OVA. The MABP drop after i.v. OVA was worsened by diphenydramine and was modestly attenuated by cimetidine, dihydroergotamine, or both together. L-NAME potentiated slightly the effects of cimetidine and dihydroergotamine by lessening the initial MABP decrease, but this transient effect was not sufficient to prevent the final collapse or to improve survival time. Decreased vasodilatory (prostaglandins E2), increased vasoconstrictory (thromboxane B2) prostaglandins, and unchanged leukotriene C4 concentrations were contributory to the overall hemodynamic changes. Thus, the combined blockade of vasodilator mediators (histamine, serotonin, and nitric oxide) slowed the MABP drop in anaphylactic shock, but did not improve survival. More studies are needed to understand these discordant effects.

Topics: Anaphylaxis; Animals; Arteries; Cimetidine; Dihydroergotamine; Dinoprostone; Eicosanoids; Enzyme Inhibitors; Heart; Histamine; Hypotension; Leukotriene C4; Male; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Ovalbumin; Pressure; Rats; Rats, Inbred BN; Receptors, Serotonin; Serotonin; Thromboxane B2; Time Factors

This study investigates the role of mast cells in the hypotension induced by antigen-mediated anaphylaxis, compound 48/80 and dextran in mast cell-deficient white spotting (Ws/Ws) and normal wild type (+/+) rats. Rats were sensitized with 10 microg of intraperitoneal ovalbumin in saline or saline alone (sham-sensitized). Sensitized rats, both Ws/Ws and +/+ but not sham-sensitized rats, challenged intravenously with ovalbumin exhibited hypotensive responses. There was no evidence of mast cell activation in rat mesentery 20 min after intravenous antigen challenge in sensitized +/+ rats. Hypotension induced by intravenous injection of dextran (Dextran-162, 6%, 2 ml kg(-1)) or compound 48/80 (1 mg kg(-1)) occurred in +/+ rats, but not in Ws/Ws rats, and was inhibited by pretreatment with a combination of chlorpheniramine and cimetidine. Taken together, these data indicate that the hypotensive response induced by antigen-mediated anaphylaxis is independent of mast cell activation, whereas mast cell amines play the main role in the hypotensive response induced by dextran or compound 48/80.

Topics: Anaphylaxis; Animals; Blood Pressure; Cell Degranulation; Chlorpheniramine; Cimetidine; Dextrans; Genotype; Heart Rate; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Hypotension; In Vitro Techniques; Injections, Intraperitoneal; Injections, Intravenous; Male; Mast Cells; Mesentery; Ovalbumin; p-Methoxy-N-methylphenethylamine; Rats; Rats, Wistar; Time Factors

X-ray contrast media (CM) toxicity resembles IgE-antigen-based anaphylaxis, and CM-related histamine release has been demonstrated in vitro and in vivo. While nobody has succeeded in producing antibodies against injections of neat CM, the ability of CM to compete with a series of antigens against their respective antibodies has recently been demonstrated. However, there is a paradox, since the CM with the strongest antibody binding are nevertheless the least likely to provoke antigen-antibody-related mast cell/basophil release.. Two strains of rats were subjected to (a) passive cutaneous anaphylaxis (PCA) studies in the presence of various concentrations of CM, (b) blood pressure (BP) tracings following bolus administrations of various prototypical CM and (c) BP tracings in ovalbumin (OVA)-sensitized rats, challenged with OVA plus CM, vs. OVA plus CM-equivalent saline.. In the PCA studies, and the OVA challenge studies, the CM appear to act in an antigen excess mode, limiting the potential of the OVA to elicit anaphylactic changes, as demonstrated by permeability studies or by BP levels. The bolus CM studies demonstrate that the more potent CM 'antigens' actually produce an increase in BP and the less potent CM 'antigens', a drop in BP. These changes can be related to the CM acting in an 'antigen' excess mode vs. an 'antigen' equivalent mode.. The CM have the potential to act in an 'antigen' excess or 'antigen'-equivalent mode. The potential to express an 'antigen'-excess mode in vivo, may be unique to CM because of the high concentrations injected.

Topics: Animals; Antigen-Antibody Reactions; Antigens; Blood Pressure; Contrast Media; Histamine Release; Hypertension; Hypotension; Ioxaglic Acid; Nitric Oxide; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred BN; Rats, Sprague-Dawley; Triiodobenzoic Acids

SR 27417, a potent PAF receptor antagonist, inhibited in a dose-dependent manner the hypotensive effect of PAF in rats. It protected rats with an ED50 value of 6 +/- 2 micrograms/kg (n = 6), when given i.v., 1 min before PAF administration. After i.v. administration, SR 27417 exhibited extended duration of action, a significant protective effect was observed up to 48 h after the administration. After i.v. injection, SR 27417 (0.3, 1 and 3 mg/kg) afforded dose-dependent protection of actively sensitized rats against ovalbumin-induced hypotension but also totally reversed established antigen-induced hypotension. These results therefore confirm that PAF plays a major role in anaphylactic shock and suggest that SR 27417 may be an effective prophylactic as well as a potent curative drug in this pathology.

Topics: Animals; Antigens; Hypotension; Male; Ovalbumin; Platelet Activating Factor; Rats; Rats, Sprague-Dawley; Thiazoles

Topics: Anaphylaxis; Animals; Histamine H1 Antagonists; Hypotension; Indomethacin; Injections, Intravenous; Kinins; Ovalbumin; Promethazine; Prostaglandin Antagonists; Prostaglandins; Rats; Serotonin Antagonists

1. Carrageenin oedema is suppressed by pre-treating the rats with cellulose sulphate, a kininogen depleting agent. This inhibition is closely related to the dose of cellulose sulphate and to the time course of kininogen depletion.2. Oedema induced by egg white or by dextran, in which the mediators are histamine and 5-hydroxytryptamine, is quite unaffected by cellulose sulphate treatment.3. Carrageenin injected intravenously lowers the arterial blood pressure of rats. This hypotensive effect is unaffected by histamine antagonists and is abolished by protease inhibitors and thus seems to be due to kinin release from plasma substrates.4. Like cellulose sulphate, carrageenin enhances the esterolytic activity of the blood from treated rats when incubated with benzoyl-arginine ethyl ester.5. The ability of carrageenin to activate the kinin-forming system could account for both its inflammatory and hypotensive effects.

Topics: Animals; Antifibrinolytic Agents; Blood Pressure; Carrageenan; Cellulose; Depression, Chemical; Dextrans; Edema; Histamine H1 Antagonists; Hypotension; Kinins; Male; Ovalbumin; Peptides; Rats; Trypsin Inhibitors

Topics: Anaphylaxis; Animals; Blood Pressure; Bradycardia; Femoral Artery; Heart Rate; Heart Ventricles; Hemodynamics; Hypotension; Ovalbumin; Rats

Topics: Agglutination; Anaphylaxis; Animals; Antigen-Antibody Reactions; Blood Circulation; Blood Pressure; Blood Transfusion; Catheterization; Drug Hypersensitivity; Heparin; Hypotension; Leukocytes; Ovalbumin; Perfusion; Rats; Vasodilator Agents