HYPOTENSIVE ACTION OF IGG PREPARATIONS CONTAINING AGGREGATES IS SUPPRESSED BY PAF-RECEPTOR ANTAGONIST BN-52021 AND BY GADOLINIUM CHLORIDE (AN AGENT BLOCKING KUPFFER CELL-FUNCTION)

The hypotensive side effect of four IgG preparations was studied in a rat model. An unmodified, chromatographically isolated preparation (prepn. C) appeared to induce a transient drop in blood pressure via the kininogen kinin system. A preparation made by ethanol fractionation (prepn. E) and an ethanol-fractionated, modified product (prepn. M) produced an action which does not depend on kininogen activation. No blocking of kininase was required for this effect and it was brought about by prepn. M was devoid of any sizeable prekallikrein activator or kallikrein like proteinase content. The effect was associated by the aggregate fraction of prepn. E, but not with IgG monomers of the same preparation. Animals given these latter types of IgG preparations were refractory to a second dose 24 hours later. The involvement of PAF in the kinin-independent hypotensive action is suggested by the finding that PAF-receptor antagonist BN 52021 prevented the effect and returned the blood pressure close to normality when given during hypotension. A blockade of Kupffer cells brough about by administration of GdCl3 was also found to prevent the effect pointing to the involvement of these type of cells in the reactions.