Vascular reactivity in diabetes mellitus: possible role of insulin on the endothelial cell

Abstract

The response to vasoactive agents of microvessels of the rat was tested in vivo by direct microscopic observation of the exteriorized mesentery and assessment of cutaneous vascular permeability changes with Evans blue. The constrictor response to a standard amount of noradrenaline in mesenteric microvessels was fully antagonized by acetylcholine in normal, diabetic, adrenalectomized and diabetic‐adrenalectomized rats. In contrast, the minimum doses of histamine or bradykinin, effective in normal or adrenalectomized animals, had to be increased about 20 fold to be active in diabetic or diabetic‐adrenalectomized animals. Topical application of insulin to mesenteric microvessels of diabetic animals, in amounts not causing any increase in serum insulin levels, improved or restored the capacity of the animals to respond to histamine or bradykinin, acting as antagonists of the vasoconstrictor response to noradrenaline. Topical insulin, however, was ineffective in normal animals given 2‐deoxyglucose, the acute effects of which result from cellular glucopaenia unrelated to insulin deficiency. Vascular permeability responses to intracutaneous histamine or bradykinin were decreased in animals pretreated with 2‐deoxyglucose as much as in diabetic animals. Pretreatment of normal animals with indomethacin produced no effect on the responses of these animals to histamine or bradykinin, tested as antagonists of noradrenaline on mesenteric microvessels, or as vascular permeability‐increasing factors in the skin. Pretreatment of normal animals with chloroquine, mepacrine or dexamethasone had no effect on the reactivity of mesenteric microvessels to histamine and bradykinin, acting as antagonists to noradrenaline. It is suggested that vasoactive substances, endowed with permeability‐increasing properties, evoke relaxation of microvessels through an insulin‐dependent action on endothelial cells, unrelated to the release of arachidonic acid metabolites. This action would lead to increased vascular permeability, with opening of interendothelial junctions, and temporary changes in composition of extravascular fluid, which in turn, would provide the basis for vasodilatation. Diabetes mellitus apparently impairs such responses as a result of the accompanying cellular glucopaenia. Adrenal corticosteroids are not involved in the impaired responses.

Eotaxin Is Specifically Cleaved by Hookworm Metalloproteases Preventing Its Action In Vitro and In Vivo

“…Both mammals and viruses encode apparently nonsignaling receptors that may sequester chemokines, preventing their actions on target cells. In addition, proteoglycans that can bind all chemokines, both at the cell surface and as part of the extracellular matrix, may be important regulators of chemokine function (38,39).…”

Mast cell changes in experimental diabetes: focus on attenuation of allergic events

“…This is still a controversial point as other investigators have suggested a direct correlation between hyperglycemia and the incidence of infection in diabetic patients (Rayfield et al 1982). A number of studies shows that diabetic animals present a decreased response to intradermally administered bradykinin and vasoactive amines as well as swelling induced by dextran, carrageenan, and cellulose sulphate, indicating alteration in the microcirculatory reactivity (Garcia-Leme et al 1974, Fortes et al 1984, Akamine et al 2003. Moreover, neutrophils from diabetics have also been shown to present functional abnormalities such as less phagocytizing capacity (Wertman & Henney 1962) and chemotactic responses (Mowat & Baum 1971, Fortes et al 1991, Mello et al 1992, which might be extended to other inflammatory cells as those involved in allergic processes.…”

Comparison between Wound Healing in Induced Diabetic and Nondiabetic Rats after Low-Level Laser Therapy

“…Before starting the experiment, the laser was calibrated using a 2-W Broadband Power/Energy Meter (model 13 PEM 001/J). The laser fluence on the rat skin was 10 J/cm 2 , corresponding to an irradiated area of 0.025 cm 2 and an exposure time of 17 sec. Wounds were irradiated at only one point, at their central region.…”

“…Complications include impaired wound healing, circulatory alterations, decreased collagen production, and skin defects. [1][2][3][4][5] It has been suggested that diabetes mellitus causes macro-and microvascular alterations, as well as neurological diseases. Some authors have demonstrated that lowlevel laser therapy (LLLT) stimulates wound healing, by increasing collagen deposition and blood flow in the wound area.…”