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

The paper considers the significance of prostacyclin-thromboxane (PGI2/TxA2) balance for cardiovascular performance in health and in angina pectoris and myocardial infarction. The functional interaction between prostacyclin and thromboxane was examined in terms of a number of risk factors for coronary heart disease (CHD), such as ageing, atherosclerosis, arterial hypertension, diabetes mellitus, obesity, hypokinesia, smoking, alcoholism, sex differences, and predisposition to the disease. A unidirectional pattern of changes in the PGI2/TxA2 balance towards TxA2 was found in CHD and in the presence of all the aforementioned risk factors. The paper discusses possible mechanisms responsible for these changes, as well as their contribution to the pathogenesis and prevention of CHD.
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PMID:[Prostacyclin-thromboxane balance and risk factors of ischemic heart disease]. 251 11

Patients with diabetes mellitus have an increased susceptibility to heart disease. The exact mechanism for this phenomenon is unclear. Abnormalities in prostaglandin (PG) production have been suggested as a possible cause. In this connection, we examined the PG synthetic capacity of cardiac microsomes from spontaneously diabetic rats. Cardiac microsomes from diabetic and control rats produced varying amounts of 6-keto-PGF1 alpha (stable degradation product of PGI2), PGE2, PGD2, PGF2 alpha, and TXB2 (stable breakdown product of TXA2). In both instances the production of 6-keto-PGF1 alpha predominated, however, microsomes from diabetic rats showed markedly greater conversion of arachidonic acid to all the PG products, especially 6-keto-PGF1 alpha. When PGF2 alpha metabolism was detected between diabetic and control heart preparations. These results show an enhanced cyclooxygenase activity in diabetic rat hearts without any change in prostaglandin dehydrogenase activity. Such a change may promote some of the cardiac alterations seen in diabetic mellitus.
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PMID:Altered myocardial prostaglandin synthesis in spontaneously diabetic rats. 251 48

The vasodepressor responses to intravenous injections of arachidonic acid, and the formation of its metabolites, were studied in rats made diabetic 1 or 2 weeks after a 1-dose alloxan treatment. Arachidonic acid dose-dependently decreased the diastolic blood pressure in normal animals, but this hypotensive effect was significantly weaker in 2-week postalloxan-treated rats. Indometacin abolished arachidonic-acid-induced depressor responses in both normal and diabetic animals. Hypotension induced by sodium nitroprusside was of the same magnitude in non-diabetic and insulin deficient rats. Plasma levels of thromboxane B2 were significantly increased in both the 1- and 2-week diabetic rats, being greater in the latter group; those of 6-keto-PGF1 alpha remained unchanged during the 2-week diabetic period. It is concluded that the attenuation by diabetes of depressor responses to arachidonic acid could be due to changes in the thromboxane/prostacyclin balance, with thromboxane formation being elevated whereas prostacyclin generation remains unaffected.
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PMID:Changes in arachidonic acid metabolite patterns in alloxan-induced diabetic rats. 251 50

Noradrenaline levels in the superior cervical ganglion and sciatic nerve were significantly reduced in chronic streptozotocin-induced diabetes in rats. Sciatic nerve sheath in vitro biosynthesis of 6-keto prostaglandin F1 alpha (6KPGF1 alpha; the stable metabolite of prostacyclin) was significantly reduced but not in acute experimental diabetes. Nerves with reduced 6KPGF1 alpha had an excessive response to arachidonic acid stimulation. We suggest that the reduced endogenous biosynthesis of prostacyclin is due to reduced substrate availability, possibly due to the reduced noradrenaline. The implications of these findings on the pathogenesis of diabetic neuropathy are discussed. Neuropathy was found to involve all fibre populations studied (motor, sensory and sympathetic) and progressed with duration of diabetes.
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PMID:Prostacyclin and noradrenaline in peripheral nerve of chronic experimental diabetes in rats. 252 6

In order to determine whether glomerular hyperfiltration in diabetes is related to renal prostaglandin production we have studied the urinary excretion of PGE2, 6-keto-PGF1 alpha, and TXB2 in two sex, age and duration of diabetes matched groups of 9 and 10 Type 1 diabetic patients with either normal (mean 121, range 105-129 ml min-1 1.73 m-2) or supranormal glomerular filtration rate (154, 135-206 ml min-1 1.73 m-2). A group of 15 matched healthy volunteers served as control subjects. Urine was collected overnight for an uninterrupted period of at least 6 h. All studies in the patients were performed during insulin-induced sustained euglycaemia to prevent the confounding effect of variable degrees of blood glucose control on urinary prostaglandin excretion. Blood pressure was normal in all subjects. Urinary excretion of 6-keto-PGF1 alpha was significantly higher in the patients with glomerular hyperfiltration (median 17.1, range 4.5-33.6 ng h-1) than in those without (8.8, 1.5-13.8 ng h-1; p less than 0.05) or in normal control subjects (9.6, 5.2-15.5 ng h-1; p less than 0.05). No significant differences were found in the excretion rates of PGE2 and TXB2 between the three groups. Under conditions of controlled plasma glucose and insulin concentrations the urinary excretion of 6-keto-PGF1 alpha, the stable breakdown product of PGI2, a compound of endothelial, possibly glomerular, origin was elevated only in the diabetic patients with glomerular hyperfiltration.
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PMID:Glomerular hyperfiltration and urinary prostaglandins in type 1 diabetes mellitus. 252 82

We examined the relationship between glomerular filtration rate (GFR), as assessed by inulin clearance, and glomerular prostaglandin and thromboxane production as a function of glycemic control in control rats and rats that had had streptozocin-induced diabetes for 2 months. In severely hyperglycemic (plasma glucose level 644 +/- 40 mg/dl) rats with streptozocin-induced diabetes that had not been treated with insulin, GFR was reduced to values below those in control rats by 2 months, whether data were expressed as milliliters per minute or as a function of kidney weight. By contrast, treatment of the diabetic rats with insulin to maintain moderate hyperglycemia (plasma glucose concentration 398 +/- 40 mg/dl) resulted in a persistent elevation of GFR compared with values in control rats. Basal production of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolic product of prostaglandin I2 (PGl2), by glomeruli isolated from the moderately hyperglycemic rats was higher than corresponding values of glomeruli from control rats. Differences in PGE2 and 6-keto-PGF1 alpha production by glomeruli from moderately hyperglycemic and control rats were abolished by addition of arachidonate to the incubation mixture, supporting a role for enhanced availability of arachidonate in the mediation of altered vasodilatory prostaglandin production. By contrast, glomerular production of thromboxane B2 (TXB2), the stable metabolic product of thromboxane A2 (TXA2), was not different in moderately hyperglycemic rats compared with controls. Thus, enhanced production of vasodilatory prostaglandins by glomeruli from moderately hyperglycemic rats was associated with an increase in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role for local prostaglandin and thromboxane production in the regulation of glomerular filtration rate in the rat with streptozocin-induced diabetes. 252 67

In rats with streptozotocin-induced diabetes antioxidant protection of diabetic angiopathy was performed by flunarizine (10 mg/kg/day) and aligeron (10 mg/kg/day), applied intraperitoneally during 2.5 months of diabetes. Diabetic vascular complications were assessed by morphologic determination of PAS-positive mucopolysaccharides and measurement of vascular wall thickness in addition to quantitative estimation of lipid hydroperoxides, thromboxane A2/prostacyclin disbalance and plasma beta-thromboglobulin changes. Both drugs prevented development of diabetic angiopathy in rats by inhibition of lipid peroxidation, prostanoid synthesis and platelet activity, but the effect of flunarizine was more pronounced, which could be explained by its additional blocking effect of abnormal calcium flux into vascular cells. The free radical scavenging action of flunarizine and aligeron was investigated.
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PMID:Streptozotocin-induced diabetes in rat. III. Antioxidant protection of vascular complications by flunarizine and aligeron. 253 Dec 58

Changes in renal perfusion pressure and eicosanoid release in response to arginine vasopressin (AVP; 1-10 ng) and angiotensin II (ANG II; 1-10 ng) were determined 5 days, 2 wk, and 8-12 wk after the induction of diabetes with streptozotocin (STZ) in male Wistar rats. Renal perfusion pressure responses to AVP and ANG II were reduced at 2 and 8-12 wk, but not at 5 days, after the induction of diabetes. However, AVP- and ANG II-stimulated release of prostaglandins into the renal venous effluent was depressed at all times tested. Inhibition of cyclooxygenase with indomethacin did not significantly influence the perfusion pressure responses to ANG II and AVP. Likewise, raising perfusate glucose levels to 400 mg/dl or adding insulin (180 microU/ml) to the perfusate failed to modify responses to ANG II. In contrast, administration of 0.3 microgram arachidonic acid (AA), a dose approaching threshold in control rat kidneys, to the kidney of the diabetic rat resulted in a marked increase in perfusion pressure. Associated with the increase in renal perfusion pressure to AA in the diabetic rat were significant increases in renal venous efflux of prostaglandin E2 and prostacyclin compared with control. These data suggest a defect in renal deacylation-reacylation of AA associated with an increase in cyclooxygenase activity in the diabetic rat.
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PMID:Renal vascular responses and eicosanoid release in diabetic rats. 253 49

This study examined the effect of short-term streptozotocin-induced diabetes in rats on the response of cremaster muscle arterioles to angiotensin II (ANG II) and vasodilatory prostaglandins. Topically applied ANG II (10(-10) to 10(-6) M) caused significantly greater vasoconstriction of third-order arterioles in diabetic animals in comparison with controls. For example, in response to 10(-6) M ANG II arterioles of the diabetic animals constricted to 43 +/- 10% of basal diameter compared with controls' 67 +/- 6% (P less than 0.05). Furthermore, the magnitude of the secondary vasodilatation after ANG II-induced constriction was decreased in diabetic animals (108 +/- 4 and 131 +/- 9%, P less than 0.025). Cyclooxygenase inhibition resulted in marked arteriolar constriction, with this effect being less evident in diabetic animals. In response to indomethacin (2.8 x 10(-5) M), arterioles of the diabetic animals constricted to 84 +/- 7% of basal diameter compared with 56 +/- 4% in controls (P less than 0.01). Arterioles of the diabetic animals were less responsive to exogenous prostaglandin I2 (PGI2) and PGE2 (10(-12) to 10(-6) M) despite evidence of increased in vitro PGI2 production. The data demonstrate potentiation of the vasoconstrictor response and a diminution of the secondary vasodilator response to ANG II in experimental diabetes. These alterations may be due, in part, to decreased responsiveness of skeletal muscle arterioles to vasodilatory prostaglandins.
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PMID:Altered microvascular reactivity in streptozotocin-induced diabetes in rats. 253 51

Platelet poor plasma thromboxane and prostacyclin levels and the quantity of metabolic control, altogether with vascular complications were evaluated in 55 children diabetes mellitus. The control group consisted of 33 healthy children of the similar age. Thromboxane levels remained unchanged in diabetics, while prostacyclin proved to be significantly decreased, which resulted in greater thromboxane/prostacyclin ratio. No meaningful differences were found according to the presence or absence of vascular complications in this group of diabetics. A positive correlation could have been detected between glycosylated haemoglobin and thromboxane levels, while a negative one between glycosylated haemoglobin and prostacyclin levels. The alterations of prostaglandin metabolism may be regarded as a consequence of diabetic metabolic changes, rather than of vascular complications. Disturbed prostaglandin metabolism in diabetic children might have a role in the pathogenesis of vascular complications.
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PMID:[Connection between plasma thromboxane and prostacyclin levels in the metabolic control of diabetic children]. 264 85


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