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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular disease in diabetics could arise in part from altered vessel wall catebolism. Specific activities of hydrolases in aortic smooth muscle cells from rats with streptozotocin-induced diabetes were measured. Enyzmes included: neutral alpha-glucosidase, alpha-mannosidase, and lysosomal N-acetyl beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 4,8, and 11 weeks of diabetes, activities of all enzymes studied were decreased significantly in diabetic vessels, decreases ranging from 15% for cathepsin C to 62% for alpha-mannosidase. After 3 weeks of diabetes, insulin treatment for 1 week restored enzyme levels to normal. After 7 weeks of diabetes, 1 week of insulin treatment did not restore enzyme levels fully to normal (acid cholesteryl esterase was unchanged); 4 weeks of insulin did. Acid phosphatase and N-acetyl beta-glucosaminidase activities were reduced markedly in histochemical studies of diabetic aortas at all time periods and were restored by insulin treatment. Alloxan-induced diabetes gave results similar to those with streptozotocin. Significant decreases of aortic hydrolase activities, including those of lysosomes, occur in experimental diabetes mellitus and could contribute to accumulation of substrates in vascular smooth muscle cells.
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PMID:Hydrolase activities in the rat aorta. I. Effects of diabetes mellitus and insulin treatment. 14 80

All agree on altered platelet function in vitro (and increasingly in vivo) in diabetics of substantial duration and/or with clinical evidence of angiopathy. However, a platelet abnormality earlier in the disease remains uncertain. Three sets of data from Oxford will be reviewed: (1) Observations of Honour on platelet aggregation at sites of minimal injury within blood vessels of anesthetized rabbits, with greater sensitivity to superfused ADP when hyperglycemia has followed alloxan only days previously. This increased aggregatability (not hyperglycemia determined) is reversed by a few days of insulin treatment or by dipyrimadole (alone or with synergistic acetyl salicylic acid): (2) Beta-thromboglobulin is released from platelets and is increased in venesected blood from diabetics after a standardized procedure (no prostaglandin E1 in anticoagulant) with final radioimmunoassay. Results in diabetics after surgery, etc., will also be presented, and (3) in a prospective study of newly-diagnosed, mostly maturity-onset type diabetics, an increase in plasma fibrinogen (thrombin coagulation of plasma, controlled against normals) was observed during the first 3 yr, largely due to males treated with sulfonylureas; decreases in platelet count and in prothrombin concentration were also statistically significant.
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PMID:Direct animal and indirect human evidence of altered platelet function in diabetics. 16 73

Diabetic vascular disease is more severe, diffuse, and accelerated when compared to nondiabetic vascular disease. Endothelial cell injury or alteration in endothelial cell function is hypothesized to be the initial cellular event in the pathophysiology of diabetic vascular disease. We examined the effect of insulin-treated and untreated alloxan diabetes on the proliferation of rabbit aortic endothelial cells in vitro by growing thoracic aortic endothelial cells from alloxan diabetic rabbits in serum obtained from alloxan diabetic rabbits. Diabetes adversely affected the proliferation of aortic endothelial cells; the most significant decrease in cell proliferation was noted in untreated diabetic cells. Crossover studies between endothelial cells and serum from different groups revealed that diabetes slows endothelial proliferation by not only a serum effect but also an intrinsic cellular effect. These observations suggest that diabetes adversely affects the proliferation of aortic endothelial cells by changing cell and serum functions.
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PMID:The effect of diabetes on the proliferation of aortic endothelial cells. 146 63

Normal and alloxan treated diabetic rabbit kidneys were perfused with Krebs-Henseleit solution in a non-recirculating system and the effects of norepinephrine (NOR) 10(-6)M were tested by infusion of this drug for three subsequent periods of 20 min each, with an interval of 10 min for drug wash-out. In the control kidneys the infusion of NOR promoted an intense vasoconstriction, which was less intense during the second and the third periods. This was known as tachyphylaxis. In contrast to the controls, kidneys from diabetic animals did not show tachyphylaxis to NOR, but when insulin was added to the perfusate, tachyphylaxis appeared. Normal kidneys perfused with hyperosmolar solutions show, as in controls, the same phenomenon. The data presented here demonstrate a defect of adrenergic vascular receptors in alloxan treated kidneys, which can be acutely reversed by insulin. These facts are of importance for the understanding of the vascular disease in diabetes.
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PMID:Alloxan diabetes blocks noradrenergic tachyphylaxis in the isolated rabbit kidney--effects of insulin. 151 84

After mentioning insulin deficiency diabetes in animals produced by drugs such as Alloxan, Diazoxide or Streptozotocin only drugs are discussed, which are used in elderly patients and may either provoke diabetes mellitus (or temporary hyperglycemia) or may change the clinical course of diabetes. In the first group endocrine products such as corticosteroids, estrogens, somatotrophic hormone, thyroid hormone, glucagon, somatostatin, catecholamines and hormones with anabolic effects are listed. The second group comprises saluretics, salicylates, amphetamines, pentamidine, nicotinic acid and its derivatives, beta-receptor blockers and finally laxatives. Hypopotassemia alone can also be the cause of hyperglycemia. Speaking of the sulfonylureapreparations, their interaction with alcohol, with phenylbutazone, with some sulfonamides and the effect of the sulfonylureas on peripheric insulin-receptors is discussed. In case of severe diabetic vascular disease the use of anticoagulants may lead to hemorrhages. If such an hemorrhage occurs in the eyes, it may lead to blindness. In diabetic nephropathy the use of phenacetine and its derivatives should be substituted by another medication. This review is not at all complete but should only show some of the problems in the treatment of elderly diabetic patients.
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PMID:[Iatrogenic diabetes mellitus (side effects and interactions of drugs during clinical diabetes mellitus (author's transl)]. 612 38

Experiments were made on albino rats with alloxan diabetes. Half of the animals received sodium ribonucleate (20 mg/100 g) per os daily for two weeks. The intensity of RNA biosynthesis was judged from 32P incorporation. It was established that insulin deficiency abolished the biosynthesis of mitochondrial, cytoplasmic and nuclear RNA in the liver and kidneys, of mitochondrial and cytoplasmic RNA in the heart muscle, and of total RNA in the aorta tissue. Oral administration of sodium ribonucleate gave rise to the increased biosynthesis of RNA in these organs. A conclusion is drawn that oral application of the drug may be used in combined treatment of diabetes mellitus in general, and of that complicated by angiopathy, in particular.
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PMID:[Action of perorally administered sodium ribonucleinate on RNA biosynthesis in the aortic, cardiac, liver and kidney tissue of animals with experimental diabetes mellitus]. 617 59

Nonarteriosclerotic (virgin) and arteriosclerotic (breeder) rats were made diabetic with alloxan. Animals were treated with constantly adjusted doses of insulin, occasionally adjusted doses, or no treatment. The obese breeder rats lost weight; the lean virgin rats gained weight. All of the animals were autopsied 5 months post-alloxan. Blood pressure increased in virgin rats; the pre-existent mildly elevated blood pressure of arteriosclerotic breeder rats decreased. Glucosuria was effectively reduced in animals accorded good control; blood glucose was not effectively controlled. Circulating nonesterified fatty acids and triglycerides were more effectively normalised by insulin therapy. The diabetes was accompanied by adrenal hypertrophy, thymus gland involution, and increased circulating corticosterone. Virgin rats (68%) developed arterial disease when made alloxan-diabetic; treatment with insulin completely prevented arterial disease. Breeder rats with pre-existent arteriosclerosis showing worsening of their cardiovascular disease; when made severely diabetic those provided with good control of their diabetes were protected against exacerbation of their vascular disease.
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PMID:Good versus moderate regulation of alloxan-induced diabetes in arteriosclerotic and nonarteriosclerotic rats. 699 26

Diabetes mellitus is a major cause of ischemic coronary artery disease. Endothelial dysfunction is implicated in the pathogenesis of diabetic vascular disease. To examine coronary blood flow (CBF) regulation with endothelium-derived nitric oxide (EDNO) in the diabetic state, we compared the effects of both acetylcholine (ACh) and adenosine (Ado) on left circumflex coronary artery (LCX) blood flow in 12 vehicle-treated and 21 dogs made diabetic with alloxan anesthetized with pentobarbital. All dogs were pretreated with aspirin to inhibit endogenous prostaglandins. None of the hemodynamic parameters were significantly different in the two groups. The percent change in coronary vascular resistance (CVR) after ACh (100 ng/kg) infusion was significantly attenuated in diabetic dogs (-56.5 +/- 1.4%) as compared with vehicle-treated dogs (-64.5 +/- 1.2%) (p < 0.01), whereas the effect of Ado (1 microgram/kg) was not different between the two groups (-71.1 +/- 1.5% in vehicle, -67.0 +/- 1.3% in diabetes). After infusion of incremental doses of NG-nitro-L-arginine methyl ester (L-NAME) 10(-5)-10(-3)M, the effect of ACh was progressively inhibited in both groups and was different no longer between the two groups after the maximal dose. L-Arginine (L-ARG), but not D-ARG, significantly restored the effect of ACh in diabetic dogs but did not affect vehicle-treated dogs. The effect of Ado did not change after L- and D-ARG administration. Cu, Zn-superoxide dismutase (Cu, Zn-SOD) had no effect on any of the effects of ACh and Ado in diabetic dogs. Regulation of CBF with EDNO is impaired in dogs with alloxan-induced diabetes, and this impairment is partially restored by L-ARG.
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PMID:Impairment of coronary blood flow regulation by endothelium-derived nitric oxide in dogs with alloxan-induced diabetes. 879 37

To study platelet-derived microparticle generation in diabetes mellitus, we injected alloxan into male Japanese white rabbits. Injection of alloxan induced diabetes, but did not cause any significant change in various biochemical and hematological parameters. However, diabetic rabbits showed a significant elevation of platelet-derived microparticles from 8 weeks after alloxan injection (week 0: 0.45 +/- 0.24%; week 8: 1.12 +/- 0.61%, p < 0.005). These microparticles are known to have prothrombinase activity, suggesting that they may promote vascular complications in diabetes and may be used as a marker of vascular disease.
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PMID:Platelet-derived microparticles in alloxan-induced diabetes in rabbits. 887 35

ATP-dependent potassium channel blockers used as hypoglycaemic agents may have effects on vascular disease in diabetes mellitus beyond their effect on blood glucose control. This study was designed to determine the effects of treatment with gliclazide on the isolated abdominal aorta of diabetic rabbits in which endothelium-dependent relaxation is impaired by a mechanism involving oxygen-derived free radicals. After induction of diabetes with alloxan, there was no effect of gliclazide (10 mg x kg(-1) day(-1) orally) on blood glucose or insulin levels over a 6 week period. Hence, this permitted an examination of the vascular effects of gliclazide in diabetic rabbits exclusive of metabolic effects. Acetylcholine- and nitric oxide-induced relaxation in aortae from rabbits treated with or without gliclazide were measured in the absence or presence of the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (L-NAME). Diabetes was associated with significant impairment of acetylcholine-induced endothelium-dependent relaxation of the abdominal aorta which was not significant in diabetic rabbits treated with gliclazide in vivo. Aortae from diabetic rabbits studied in the presence of L-NAME showed an exaggerated contraction to acetylcholine which was prevented in rabbits treated with gliclazide. Gliclazide treatment did not affect the response to acetylcholine of normal rabbit aorta, and gliclazide when added in vitro had no effect on the response of diabetic rabbit aorta, suggesting that the effect of gliclazide was specific to the abnormality arising with diabetes and was not due to an acute effect of the drug. These data indicate that gliclazide, aside from either a direct antioxidant action or an effect on insulin or glucose levels, may ameliorate diabetic endothelial cell dysfunction.
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PMID:Vascular action of the hypoglycaemic agent gliclazide in diabetic rabbits. 949 23


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