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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years it has become apparent that endothelial cells have important implications in the regulation of vascular smooth muscle tone, vascular permeability and platelet reactivity. One important physiological feature of these cells is the formation of the endothelium-derived relaxing factor (EDRF). This short-lived compound is a potent vascular smooth muscle relaxant and it also inhibits platelet aggregation and adhesion to the vessel wall. Its active principle seems to be nitric oxide (NO), and consequently it can be regarded as the "endogenous nitrovasodilator". In addition to EDRF, endothelial cells synthesize prostacyclin which also has platelet antiaggregatory and vasodilator properties. A reduced effectiveness of the EDRF mechanism is implicated, especially in those events of the vascular pathophysiology associated with an increased vascular tone or vasospasm. For example, a reduced production and/or action of EDRF has been found in animal models of atherosclerosis as well as in atherosclerotic human coronary arteries. In addition, prostacyclin production is reduced under these conditions. In different animal models of hypertension and diabetes mellitus, endothelium-mediated relaxation is also found to be reduced. In addition, under certain pathophysiological conditions, the endothelium seems to produce vasoconstrictor material.
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PMID:[Endothelial functions in cardiovascular diseases]. 265 5

In the present study the effects of a short term intensive glycaemic control obtained with subcutaneous insulin therapy on lipids and apoprotein levels, platelet aggregation, platelet sensitivity to prostacyclin and platelet thromboxane production were investigated in 20 patients with type 2 diabetes and vascular disease. In 11 out of the 20 patients there was a significant improvement of glycaemic control (fructosamine reduction). Only with tight improvement of glycaemic control there was significant change in the concentration of ADP and collagen required to produce 50% of the maximum aggregation wave response, in the responsiveness of platelet to PGI2 and in the TxB2 synthesis. Lower Apo B levels were also shown in the tight control group suggesting that Apo B changes may have influenced platelet aggregation and thromboxane synthesis.
Diabetes Res 1989 Jan
PMID:Platelet function in patients with type 2 diabetes mellitus: the effect of glycaemic control. 266 42

This experiment was conducted to determine the effect of diabetes on uterine prostanoids production in near-term rats. The incidence of an insulin therapy was also studied. On the 21st day of pregnancy, uterine PGE2, PGF2 alpha and PGI2 levels showed a significant increase (respectively p less than 0.05, p less than 0.01 and p less than 0.05) in diabetic rats compared to controls whereas TxA2 production remained unchanged. The insulin therapy restored PGE2 levels, the most potent stimulatory factor of the myometrial fiber at control values, whereas it enhanced significantly PGI2 concentrations (p less than 0.05) and had no effect on PGF2 alpha production; TxA2 levels remaining always unchanged. It is suggested that the increase in uterine protanolds production during diabetes could induce a myometrial hypertonicity and play a role in the disturbances of the fetal development. The maintenance of PGE2 levels to control values by the insulin therapy might contribute to a normal delivery.
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PMID:Increase in uterine prostaglandin E2, F2 alpha, prostacyclin and stability in thromboxane A2 production during late pregnancy in streptozotocin-induced diabetic rats. 267 12

The addition of prostaglandin I2 (PGI2) enhanced the adhesion of red cells from normals and patients with diabetes mellitus or sickle cell anemia (SCA) to human cultured endothelial cells (p less than 0.025). The maximal effect was reached with 10(-11) M PGI2 after 30 min incubation. Red cell adhesion was also increased by PGD2 but PGE1 and 6-keto-PGF1 alpha had no significant effect. Since enhanced adhesion of red cell to endothelium and increased red cell calcium content have been proposed to be related in SCA, we have investigated the calcium binding to human resealed normal erythrocyte membrane by using (45Ca) calcium in presence of the different PG which alter red cell adhesion or not. Calcium binding was time-dependent and potentiated in presence of PGI2 (p less than 0.01) but not of PGD2. The fact that erythrocyte adhesion is enhanced by both PGI2 and PGD2 while calcium binding is increased only by PGI2 suggests that the two phenomenon can be dissociated.
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PMID:Modification of membrane properties of erythrocytes by PGI2. 267 83

The reactivity to methoxamine (Met) of atria isolated from the hearts of normal and from acutely streptozotocin-diabetic rats has been studied. Met (1 X 10(-6) M) increased the tension of both normal and diabetic atria, but in diabetic atria, the dose-response curve to Met was shifted to the left and the efficacy of Met was enhanced. Inhibitors of alpha-adrenoceptors blocked, in a competitive manner, the positive inotropic effect induced by Met in both types of atrial preparations. Inhibitors of the cyclo-oxygenase pathway for arachidonic acid metabolism blocked the atrial response to Met in non-diabetic as well as in diabetic atria. The inhibition of prostacyclin synthetase prevented the effect of Met in normal atria, while blockers of thromboxane generation inhibited it in diabetic ones. Agents that inhibit the activity of lipoxygenase(s) significantly reduced the positive inotropic action induced by Met in diabetic atria but failed to modify it in non-diabetic preparations. These results show that diabetic atria are more sensitive to Met than normal atria. In diabetes the response to alpha-adrenoceptor stimulation could be mediated by oxidative product generated via thromboxane synthetase and lipoxygenase(s) activities; whereas in normal preparations the action of Met may involve the release of prostacyclin.
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PMID:Hypersensitivity to methoxamine in atria isolated from streptozotocin-induced diabetic rats. 286 7

The discovery that monoamine nerves end on the central microvessels of the choroid plexus, pia-arachnoid and parenchyma has prompted an intense investigation as to their physiological and neuropathological roles. The source of the monoamine fibers to the pial vessels and choroid plexus was shown to be the superior cervical ganglion. Ganglionic stimulation causes vasoconstriction or vasodilation of pial vessels, an event depending upon the functional ratio of alpha to beta adrenergic receptors. Moreover, stimulation of the superior cervical ganglion evokes an inhibition of cerebrospinal fluid formation in choroid plexus. The locus coeruleus is the site of adrenergic nerve supply to the parenchymal capillaries and stimulation of this nucleus increases capillary permeability to small molecules and water. Neurotransmitter receptors (adrenergic, histamine, adenosine, dopamine, prostacyclin, prostaglandins and specific amino acids or neuropeptides) have been identified on microvessels and in many instances these transmitter actions are coupled to cyclic AMP synthesis. Moreover, cyclic AMP has been shown to increase the rate of capillary endothelial pinocytosis and produce brain edema. In small vessels containing smooth muscle cells cyclic AMP production improves cerebral blood flow via an initiation of vasodilatory processes. The presence of receptors for serotonin and acetylcholine have likewise been demonstrated to occur on cerebral microvessels. Limited information is available as to the receptor coupled actions of these two transmitters, but cholinergic mechanisms may act to restrict catecholamine-induced formation of cyclic AMP. Altered sensitivity of microvessels to neurotransmitters has been demonstrated following conditions of stroke, hypertension, aging, diabetes and X-irradiation.
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PMID:Neurochemical coupled actions of transmitters in the microvasculature of the brain. 287 36

Before the onset of histologically detectable alterations in diabetic arteries, a considerable decrease in vasodilatory potential is seen. While analyzing this phenomenon, the role of altered PGI2 synthesis in rings of coronary arteries from metabolically healthy and alloxan-diabetic dogs was measured by radioimmunoassay during baseline, under the influence of phenylephrine (100 mumol/L), and during hypoxia with or without the presence of the alpha adrenergic blocker phentolamine (5 mumol/L). Basal levels of PGI2 synthetized by healthy and diabetic coronaries were no different (7.9 +/- 2.1 and 6.4 +/- 1.4 pg/mg vessel). Phenylephrine potentiated PGI2 synthesis in controls (150 +/- 22%), while it proved to be ineffective in the diabetic animals (98 +/- 6%). Under hypoxic conditions, PGI2 production of healthy coronaries (152 +/- 24%) increased, while that in the diabetic ones (82 +/- 7%) decreased (p less than 0.01). In the presence of phentolamine no difference could be detected between the two groups. Given all these data, the decreased ability of the diabetic coronaries to vasodilate develops due to diminished PGI2 production, presumably controlled by adrenergic mechanisms. Furthermore, the more severe outcome of ischaemic heart disease in diabetes mellitus might be explained by the lack of an enhanced coronary PGI2 synthesis under hypoxic conditions.
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PMID:Effects of hypoxia and adrenergic stimulation induced alterations in PGI2 synthesis by diabetic coronary arteries. 289 80

Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release and by quantifying metabolism of exogenous [1-14C]arachidonic acid by thoracic aortic rings and minced cremaster muscle. The cremaster muscles from diabetic rats released significantly greater quantities of PGE2 and 6-keto-PGF1 alpha and PGE2. In contrast, the aortas from diabetic rats released smaller quantities of 6-keto-PGF1 alpha and PGE2 and exhibited reduced 6-[1-14C]keto-PGF1 alpha. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis.
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PMID:Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats. 293 95

Diabetes has been shown to result in reduced prostacyclin synthesis by macrovascular tissue in rats and humans. Other studies have shown that plasma levels of 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) and synthesis of 6-keto-PGF1 alpha by isolated glomeruli are either unchanged or increased in diabetes. Thus, microvascular tissue may respond differently to diabetes than macrovascular tissue. Accordingly, we have studied the effects of streptozotocin-induced diabetes mellitus on prostaglandin synthesis by rat cerebral microvessel (RCMV). Prostaglandin synthesis from both endogenous and exogenous arachidonic acid was determined. The yield of RCMV from diabetic and control animals was similar. Under basal conditions and following stimulation of prostaglandin synthesis by melittin (5 micrograms/ml), RCMV production of prostacyclin (measured as immunoreactive 6-keto-PGF1 alpha) was greater than production of PGE2. Both 6-keto-PGF1 alpha and PGE2 production under basal and stimulated conditions were found to be similar for control and diabetic RCMV. The RCMV converted exogenous [3H]arachidonic acid predominately to PGD2 and to a lesser extent to 6-keto-PGF1 alpha. No significant differences in the conversion of exogenous [3H]arachidonic acid to PGD2 and 6-keto-PGF1 alpha was observed between control and diabetic RCMV. This study suggests that the effect of streptozotocin-induced diabetes mellitus on prostaglandin formation by microvascular endothelium is different from its effect on macrovascular tissue.
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PMID:Effect of streptozotocin-induced diabetes on prostaglandin production by rat cerebral microvessels. 294 Jul 27

Exercise and physical conditioning may reduce the subsequent risk of major vascular thrombotic events. In view of this, it may be important to examine the effects of exercise on the blood coagulation system. The present paper reviews the effects of physical exercise and conditioning on blood coagulation, platelet function, and fibrinolytic activity. A hypothetical scheme is developed, in which increased blood coagulability and activated platelet function is counterbalanced by increased fibrinolytic activity and endothelial prostacyclin release. Some consideration is given to how this sequence of events may be altered in vascular disease states.
Diabetes Metab Rev 1986
PMID:Effects of exercise on platelet function, coagulation, and fibrinolysis. 294 Dec 54


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