Quantitative physiological and morphological aspects of microvascular permeability changes induced by histamine and inhibited by terbutaline.

Abstract

Histamine induced changes in microvascular permeability to macromolecules were studied in two models, the hamster cheek pouch and the canine forelimb preparation. Fluoresceinlabelled dextran FITC‐dextran. Mw=70000 and 150000 was used as tracer of permeability increases. Studies in the hamster showed that morphological changes as indicated by intravital microscopy of FITC‐dextran leakage at postcapillary venules were accompanied by an increased concentration of FITC‐dextran in the superfusion solution for the cheek pouch. Following histamine challenge during 4 min the cheek pouch microcirculation was normalized 30 min later both with regard to number of leakage sites and the concentration of FITC‐dextran in the superfusion solution. Pretreatment of the cheek pouch with terbutaline (3.6 × 10‐6 M) for 1 h resulted in total inhibition of both morphologically and fluorometrically recorded changes from continuous histamine superfusion. When terbutaline and histamine were given at the same time, there was a significant inhibition of the histamine induced increase in the number of leakage sites to 10% of the pre‐terbutaline response. The fluorometrically detected efflux of FITC‐dextran was 65% of the preterbutaline value. The dynamics of interendothelial cell gap formation and closure was also studied in the dog. Intra‐arterial infusions of histamine into forelimbs perfused at a constant pump controlled flow rate produced decreases in perfusion pressure, increases in lymph flow, lymph protein concentration, total protein transport and weight. FITC‐dextran was given as an i. v. injection 30 min before and 0, 30 and 60 min after the start of a 90 min arterial infusion of histamine into the brachial artery of the forelimb. Lymph (CL) and plasma (Cp) concentrations of FITC‐dextran were determined and CL/Cp‐ratios showed that the permeability increasing effect lasted less than 30 min although histamine was given for further 60 min. The results of both hamster and forelimb experiments suggest that leakage sites or interendothelial cell gaps in postcapillary venules are closed within 30 min from the first exposure to histamine, probably within 15 min and that there is little indication of any remaining increase in macromolecular permeability via any other route (vesicular) following closure of gaps.