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Pharmakologische Charakterisierung der vasculÄren Schrankenfunktion gegenüber Erythrocyten und Albumin

Pharmacological differentiation of vascular barriers against erythrocytes and protein

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Summary

  1. 1.

    Rabbits first received51Cr labelled erythrocytes and then125J-labelled human serum albumin intravenously, followed by the intracutaneous administration of the agents to be tested. The skin areas were excised and evaluated for escape of albumin and red blood cells. Three modes of vascular alteration have been distinguished:

  1. a)

    Increase of permeability for solutes, but not for erythrocytes, as caused by histamine and bradykinin (type I).

  2. b)

    True haemorrhage, as induced by collagenase or the snake venom factor called HR1. No prior increase of albumin permeability has been observed when following the dependence of collagenase action on time or when measuring the ratio between dose and effect, which is linear. Haemorrhage is always accompanied by escape of some additional protein (type II).

  3. c)

    Alterations of a mixed type, as caused by trypsin and chymotrypsin, to a lesser extent by the tenside lysolecithin. Haemorrhage is preceded and accompanied by massive leakage of albumin. For trypsin and chymotrypsin, the dose response ratio is semilogarithmic over a wide range, whereas for lysolecithin it is linear.

    Hyaluronidase is ineffective in rabbit vessels but enhances the escape of albumin in rats. Histamine release may be relevant as intermediary step since systemic pretreatment with mepyramine is partially preventive.

  1. 2.

    In order to correlate the in vivo findings with biochemical changes, glomerular basement membranes from rats were incubated with the agents mentioned. The release of proteins and peptides was measured by a modification of Folin's method.

  1. a)

    Bradykinin, histamine, and hyaluronidase are ineffective.

  2. b)

    The tenside lysolecithin solubilizes proteins and peptides when applied in high concentrations only.

  3. c)

    Collagenase and HR1 are about equieffective.

  4. d)

    Trypsin and chymotrypsin are about ten times more active than collagenase and HR1.

  1. 3.

    Therefore, haemorrhage and increase of albumin permeability are two clearly distinct phenomena. Our results support the following working hypothesis: Haemorrhage is due to damage of the stabilizing apparatus of the vessel, e.g. basement membranes and surrounding fibrils; the barrier for albumin, however, is to be sought in the endothelial layer of typical capillaries.

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Authors and Affiliations

  1. Pharmakologisches Institut der UniversitÄt Gie\en, Deutschland

    D. Just, D. Urbanitz & E. Habermann

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  1. D. Just
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  2. D. Urbanitz
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  3. E. Habermann
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Additional information

Herrn Dr. Ohsaka, Tokio, danken wir für HR1, Herrn Doz. Dr. Hegner, Gie\en, für die Anleitung zur PrÄparation der Basalmembranen. Herr Dr. RÄker unterstützte uns bei der Arbeit mit Isotopen. Das Auto-Gamma-Spektrometer war eine Leihgabe der Deutschen Forschungsgemeinschaft.

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Just, D., Urbanitz, D. & Habermann, E. Pharmakologische Charakterisierung der vasculÄren Schrankenfunktion gegenüber Erythrocyten und Albumin. Naunyn-Schmiedebergs Arch. Pharmak. 267, 399–420 (1970). https://doi.org/10.1007/BF00997277

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  • DOI: https://doi.org/10.1007/BF00997277

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