Influence of diabetes upon the inflammatory response of the rat. A pharmacological analysis

Leme, J. Garcia; Hamamura, L.; Migliorini, R H; Leite, M. P.

doi:10.1016/0014-2999(73)90246-x

Cited by 65 publications

(35 citation statements)

References 12 publications

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“…This phenomenon could be associated with functional changes in the behavior of microvessels [23]and/or decreased responsiveness of endothelial cells to vasoactive agents [24]. In fact, a number of studies reported that diabetic animals present a decreased response to intradermally administered bradykinin and vasoactive amines [25]as well as swelling induced by carrageenan, cellulose sulfate and antigen stimulation [26]. Alternatively, the refractoriness of diabetic sensitized rats to allergen challenge could be accounted for by a defective response of the IgE-mast cell system.…”

Section: Discussionmentioning

confidence: 99%

Adoptive Transfer of Mast Cells Abolishes the Inflammatory Refractoriness to Allergen in Diabetic Rats

Barreto

Carvalho²,

Diaz³

et al. 2003

Int Arch Allergy Immunol

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Mast cells are pivotal secretory cells primarily implicated in allergen-evoked inflammatory responses and are downregulated following experimental chemical diabetes. Here we tested the hypothesis that a decrease in the number and reactivity of mast cells would account for the hyporesponsiveness of diabetic rats to allergen-induced inflammation. We found that the anaphylactic release of histamine from sensitized ileum, trachea and skin tissues was clearly reduced in rats turned diabetic via intravenous administration of alloxan. Likewise, actively and passively sensitized diabetic rats mounted a weaker allergen-evoked pleural mast cell degranulation and protein extravasation, as compared to sensitized nondiabetic animals, which paralleled a marked reduction in the mast cell population in the pleural cavity. The number of mast cells enumerated in the mesentery from diabetic rats was also clearly reduced. The allergen-evoked plasma leakage in diabetic rats was restored by the transfer of mast cells from sensitized nondiabetic rats. Moreover, the adoptive transfer of sensitized mast cells from diabetics to naive animals led to a lower allergen-induced exudation as compared to the response noted after the transfer of sensitized naive mast cells. Purified mast cells from diabetic rats were hyporesponsive to antigen and compound 48/80 stimulation in vitro as attested by histamine release. Thus, our results show that the phenomenon of refractoriness of diabetic animals to allergen challenge appears to be accounted for by a reduction in the number and reactivity of mast cells.

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Section: Discussionmentioning

confidence: 99%

Adoptive Transfer of Mast Cells Abolishes the Inflammatory Refractoriness to Allergen in Diabetic Rats

Barreto

Carvalho²,

Diaz³

et al. 2003

Int Arch Allergy Immunol

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“…This is indicated by the finding that experimental diabetes resulting from subtotal pancreatectomy or alloxan administration leads to decreased inflammatory responses to chemical and physical stimuli and to reduced vascular permeability reactions to intradermally injected histamine, bradykinin or 5-HT. These defects were corrected by insulin administration (Garcia Leme et al 1973;Llorach et al 1976). It is plausible, therefore, that insulin is involved with the reactivity of microvessels and that its action ultimately reflects the adequate utilization of glucose by the reacting structures.…”

Section: Discussionmentioning

confidence: 99%

Influence of diabetes on the reactivity of mesenteric microvessels to histamine, bradykinin and acetylcholine

Fortes

Leme

Scivoletto

1983

British J Pharmacology

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1 Noradrenaline (NA) evoked a vasoconstrictor response in rat mesenteric microvessels in situ, the latency and nature of which was analogous in normal and alloxan-diabetic animals. 2 Histamine and bradykinin (Bk) were capable of antagonizing the response to NA in normal but not in diabetic animals. In contrast, acetylcholine (ACh) was equally effective as an antagonist to NA in both groups of animals. 3 The altered responses to histamine and Bk were not associated with hyperglycaemia since fasting rendered the diabetic animals normoglycaemic and yet did not restore the reactivity of microvessels. Previous administration of insulin to diabetic animals corrected the impaired responses to histamine and Bk.4 A similar condition of impaired responses to histamine and Bk was produced in normal animals by the intravenous injection of 2-deoxyglucose although ACh remained fully active. 5 Apparently, the functional changes observed in the response to histamine or Bk, as antagonists of the vasoconstrictor reaction to NA, were not associated with a defective response of all smooth muscle. First, because ACh remained active in diabetic animals, and, second, because extravascular smooth muscles obtained from either normal or diabetic rats were equally relaxed by histamine or Bk in vitro.6 It is suggested that histamine and Bk antagonized the vasoconstrictor response of microvessels to NA through an action on lining endothelial cells resulting in increased vascular permeability and hyperosmolarity of extracellular fluids. 7 The process depended on the availability of insulin, and, therefore, might be affected by intracellular glucopaenia as occurring in diabetes. 8 Intracellular glucopaenia markedly affected other structures. Reduced atria rates were observed in diabetes, despite the fact that the isolated preparation responded normally to NA, ACh or tyramine. Partial substitution of glucose in the bathing fluid by 2-deoxyglucose or addition of NaF to the organ bath evoked similar changes in atria from normal animals.9 ACh which has little effect on vascular permeability must exert its vasodilator effects through mechanisms which are different from those influenced by the biochemical changes occurring in diabetes.

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“…Abnormalities of microvascular responsiveness to in vascular responses to drugs (Furchgott & Zawadzchemical, physical and neurohumoral agents occur in ki, 1980;Chand & Altura, 1981a; Van de Voorde & diabetes mellitus (Garcia Leme et al, 1973;1974Leusen, 1982). An acute effect of insulin on enAltura et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

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

Fortes

Leme

Scivoletto

1984

British J Pharmacology

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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.

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Influence of diabetes upon the inflammatory response of the rat. A pharmacological analysis

Cited by 65 publications

References 12 publications

Adoptive Transfer of Mast Cells Abolishes the Inflammatory Refractoriness to Allergen in Diabetic Rats

Adoptive Transfer of Mast Cells Abolishes the Inflammatory Refractoriness to Allergen in Diabetic Rats

Influence of diabetes on the reactivity of mesenteric microvessels to histamine, bradykinin and acetylcholine

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

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