Vascular reactivity in diabetes mellitus: role of the endothelial cell

Abstract

1 The response to vasoactive agents of microvessels in situ and large arteries in vitro was compared in normal and alloxan-diabetic rats. 2 Noradrenaline was equally effective in evoking a constrictor response of mesenteric microvessels in normal and diabetic animals. 3 The constrictor response to a standard amount of noradrenaline in such vessels was fully antagonized by acetylcholine or papaverine, the minimum effective doses being equivalent in normal and diabetic animals. In contrast, the minimum doses of histamine or bradykinin, effective in normal animals, had to be increased about 20 fold to be active in diabetic animals. 4 Increased osmolarity of extracellular fluid caused a significant and equivalent increase in latency of the vasoconstrictor response of microvessels to noradrenaline in normal and diabetic animals. 5 Concentration-effect curves, constructed from the response of isolated aortae to noradrenaline, were similar in normal and diabetic animals, provided the endothelium was removed. Diabetes only affected preparations in which the endothelium was left intact. In these, the median effective concentrations of noradrenaline were greatly increased in comparison with normal values. 6 Precontracted aortae from normal and diabetic animals were equally relaxed by acetylcholine and histamine, provided the endothelium was left intact. Loss of the relaxant response of the preparations in all groups of animals was observed following removal of endothelial cells. 7 It is suggested that different mechanisms may be involved in the effects of vasodilator agents on large arteries in vitro or small vessels in situ. Histamine and bradykinin which are potent permeability-increasing factors, may antagonize the vasoconstrictor response of microvessels to noradrenaline through an action on endothelial cells with increased vascular permeability and temporary changes in composition of extracellular fluid. The reactive process of endothelial cells to permeability factors was affected by diabetes mellitus. However, the response of microvessels to acetylcholine and papaverine which are devoid of permeability-increasing properties, was not influenced by diabetes.

Modulatory role of the vascular endothelium in the contractility of human isolated internal mammary artery

“…This has been particularly shown for noradrenaline (Cocks & Angus, 1983;Fortes et al, 1983;Konishi & Su, 1983;Egleme et al, 1984) and for histamine (Van de Voorde & Leusen, 1983;1984;Griffith et al, 1984;Miller & Vanhoutte, 1986;Sercombe et al, 1986). In some instances these two agonists have been proved to stimulate EDRF release (Cocks & Angus, 1983;Van de Voorde & Leusen, 1983;Miller & Vanhoutte, 1985).…”

Endothelial dysfunction in diabetes

“…Whereas di erences in diabetes model and in duration or severity of diabetes undoubtedly play a role in some of the discrepancies, the type of circulation, the size of the vessel and the conditions of study may be a much more important source of disparity. This has been typically illustrated by the presence of impaired endothelium-dependent vasodilatation in vivo in the mesenteric circulation or in the isolated perfused mesentery of diabetic rats, and by its absence in the isolated aorta of the same animals (Fortes et al, 1983;Taylor et al, 1994b). Similarly, bradykinin-mediated vasodilatation was depressed in the hindquarters vasculature, but was normal in the kidney and mesenterium of the same diabetic rats (Ki et al, 1991).…”

Impaired sensory‐motor nerve function in the isolated mesenteric arterial bed of streptozotocin‐diabetic and ganglioside‐treated streptozotocin‐diabetic rats

“…Several studies have claimed that endothelial cells are adversely affected by diabetes, impaired endothelium-dependent relaxations having been demonstrated in clinical (De Tejada et al, 1989) and experimental (Takiguchi et al, 1988;Kamata et al, 1989;Mayhan, 1992;Miyata et al, 1992;Taylor et al, 1992) diabetes. On the other hand, supersensitivity (Gebremedhin et al, 1987;White & Carrier, 1990) and no change (Fortes et al, 1983;Gebremedhin et al, 1987;Andersson et al, 1992;Furman & Sneddon, 1993) in endothelial responses in diabetes have also been described. The function of the underlying vascular smooth muscle in diabetes is generally unimpaired.…”