Gill, Dalvir; (1991) Histamine metabolism in diabetes mellitus and vascular disease. Doctoral thesis (Ph.D), University of London, Royal Free Hospital School of Medicine.

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Abstract

The studies reported in this thesis consist of investigations of histamine metabolism in (a) various tissues and plasma of diabetic rats, and (b) in the leucocytes, platelets and plasma of patients with diabetes mellitus (DM) and peripheral occlusive vascular disease (PVD). In addition, we have investigated the factors influencing histamine uptake by normal human platelets. In DM rats histamine synthesis, as reflected by histidine decarboxylase activity, was found to be markedly elevated in the aortae and various other tissues; there was no concomitant alteration in histamine degradation. This was accompanied by a significant increase in plasma histamine concentrations. One of the likely consequences of elevated plasma and aortic histamine in DM rats would be an increase in vascular endothelial permeability. However, unlike previous reports, elevations in aortic permeability in our DM rats was not affected by the in vivo administration of either H1 or H2 receptor antagonists. In DM and PVD patients, there was a marked increase in plasma histamine concentrations. In PVD platelets there was a concomitant increase in the histamine content of leucocytes and platelets, without any alteration in histamine synthesis or breakdown. It is therefore likely that increased intraplatelet and intraleucocyte histamine in PVD is due to increased uptake by these activated cells from a 'histamine rich' plasma. We also observed an accelerated platelet histamine uptake in vitro as a result of mild platelet activation. Our studies indicate marked alterations in histamine metabolism in both experimental DM and in patients with DM and vascular disease. It is likely that an altered histamine status in the plasma and blood vessels contributes to increased vascular permeability in DM and vascular disease. Since increased vascular permeability is one of the key events in the pathogenesis of diabetic microvascular disease and atherosclerosis, it is possible that histamine plays an important role in the pathogenesis of these conditions.

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