Bradykinin and Oedema Formation in Heated Paws of Rats

Self Cite

1. Sodium phenylbutazone, soya bean trypsin inhibitor, or the concomitant administration of ascorbic acid and mepyramine protected rats against anaphylactic shock at 10 days after sensitization but gave no protection against anaphylaxis at 20 days. 2. During anaphylactic shock in rats at 10 days after sensitization, the plasma bradykinin and bradykininogen levels, as well as those in the intestinal lumen and peritoneal cavity, were markedly raised. 3. The results support the hypothesis that there are two phases in anaphylaxis in the rat-an early phase in which bradykinin is a mediator and against which phenylbutazone or soya bean trypsin inhibitor or the mixture of ascorbic acid and mepyramine, give protection, and a late phase which does not involve bradykinin.During anaphylaxis in the rat bradykinin is formed and released in large quantities (Dawson, Starr & West, 1966). Histamine does not appear to play a major role in this type of shock as the specific antihistamine drug, mepyramine, fails to protect the animal. 5-Hydroxytryptamine also may not be involved, although its toxicity like those of bradykinin and histamine is greatly increased during the period of maximal sensitization (Sanyal & West, 1958).We have now examined the effects of another group of antagonists on the severity of anaphylactic shock in the rat, and then studied changes in the kinin and kininogen levels in certain body fluids and tissues during anaphylaxis. MethodsGroups of ten or more male or female Wistar albino rats weighing 120-150 g were obtained from Fison's Ltd (Holmes Chapel). They were allowed free access to food and water.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Further evidence for the involvement of kinin in anaphylactic shock in the rat

Starr

West

1969

Self Cite

“…Moreover, the addition of calcium to the bathing fluid in supra-physiological amount actually caused depolarization. Most (Hava & Hurwitz, 1973 (Starr & West, 1967 …”

Section: Discussionmentioning

confidence: 99%

EFFECT OF ANTI‐INFLAMMATORY DRUGS ON THE MEMBRANE POTENTIAL OF VASCULAR ENDOTHELIAL CELLS in vitro

Northover

1975

1Cells of the aortic endothelium isolated from the guinea-pig and bathed at 370 C with a calcium-free superfusion fluid had membrane potentials of -41 ± 7 mV (mean ± s.e. mean). 2 Depolarization was produced by addition of potassium (50-200 mM) 6 Exposure to histamine (100 jig/ml) or heating to 450 C for 1 h caused depolarization in the presence but not in the absence of calcium. Subsequent removal of histamine or cooling again to 370 C in the continued presence of calcium permitted only slow and partial repolarization. However, repolarization was more rapid and complete in the presence of indomethacin (0.25 mM). 7 Heating to 450 C for 5 h in the presence of calcium caused progressive and almost complete depolarization. Lanthanum, cinchocaine, indomethacin, flufenamic, meclofenamic and salicylic acids, phenylbutazone and aminopyrine each reduced the depolarization, but hydrocortisone, chloroquine, benzindamine, isoprenaline and aminophylline did not.

“…Other workers deny that kinin formation participates in the response to thermal damage. Although Urbanitz, Sailer & Habermann (1970) confirmed the activation of the plasma kinin-forming system in thermal injury (Rocha e Silva & Antonio, 1960;Starr & West, 1967), they concluded that this activation was not responsible for the development of oedema.…”

Section: Introductionmentioning

confidence: 99%

In vivo effects of cellulose sulphate on plasma kininogen, complement and inflammation

Eisen

Loveday

1971

Summary1. The in vivo action of cellulose sulphate was studied in an attempt to clarify the role of complement and kinin formation in inflammation.2. Inflammatory oedema was produced in the rat paw by heat (45.50 C), and on the ear by xylene. The oedema was assessed by comparing the ratio of fresh wet weight to dry weight of corresponding injured and non-injured parts. 3. Following cellulose sulphate (6 5 mg/kg i.v.), plasma kininogen concentrations were promptly reduced by 90% or more. The reduction in complement titres was statistically significant and ranged from 17 to 65%. No toxic effects were observed. The oedema caused by heat or xylene was not reduced in these rats. 4. Cellulose sulphate (80 mg/kg i.p.) given over 3 days depleted plasma kininogen by about 90%, but reduced complement titres only slightly. These rats gained less weight and their condition was poor. Blood clotting was impaired and widespread haemorrhages were found. Heat and xylene produced significantly less oedema than in control rats. This diminished response is attributed to toxic side effects of cellulose sulphate, rather than depleted plasma kininogen and reduced plasma complement. 5. The results suggest that the inflammatory reactions to thermal and chemical injury can fully develop when plasma kininogen and complement are lowered.