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

Basal nitric oxide (NO) production and NO responses to carbamylcholine (CCh) and the Ca2+ ionophore A23187 were measured with a NO electrode in glomeruli isolated from 2 to 3-month-diabetic versus age-matched control rats. In the presence of CCh or A23187, NO production was markedly reduced in glomeruli from diabetic versus control rats. Spontaneous generation of NO by s-nitrosopenicillamine (SNAP) was also reduced in the presence of glomeruli from diabetic rats as compared with values either in control glomeruli or in buffer alone. The results demonstrate an impairment of NO generation and/or stability in glomeruli from 2 to 3-month-diabetic rats, which correlates with the previously observed suppression of NO-dependent glomerular cyclic guanosine 3',5'-monophosphate (cGMP) induced by diabetes.
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PMID:Impaired nitric oxide release by glomeruli from diabetic rats. 778 50

Patients with insulin-dependent diabetes mellitus are at high risk for vascular disorders such as hypertension, nephropathy, and retinopathy. The most common cause of morbidity and mortality in patients with insulin-dependent diabetes is vascular disease. Despite ongoing research, the pathogenesis of vascular disease in diabetes remains unclear. In recent years, numerous investigators have examined the role of the endothelium-derived relaxing factor, nitric oxide, in the disease state of hypertension and its complications. We review the role of nitric oxide in the development of diabetes-related vascular disease and discuss findings suggesting that nitric oxide metabolism and vascular responsiveness to nitric oxide are altered in diabetes. Patients with diabetes may benefit from therapy that addresses this pathogenic deficiency.
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PMID:Role of nitric oxide in insulin-dependent diabetes mellitus-related vascular complications. 778 58

Vascular endothelial injury associated with arterial narrowing leads to platelet adhesion and aggregation at the site of endothelial injury and to the local accumulation of several mediators that promote platelet aggregation and vasoconstriction, including thromboxane A2, serotonin, adenosine diphosphate, platelet activating factor, oxygen-derived free radicals, activated thrombin, and tissue factor. At the same sites of endothelial injury, there is a reduction in absolute or relative amounts of the endogenous inhibitors of platelet aggregation and vasoconstriction, including prostacyclin, endothelium-derived relaxing factor (nitric oxide), and tissue plasminogen activator; the loss of the effects of the endogenous inhibitors preventing platelet aggregation and vasoconstriction helps to create a prothrombotic and vasoconstrictive environment. Endothelial injury occurs as a result of atherosclerotic plaque fissuring or ulceration, flow shear stress, hypertension, diabetes mellitus, immune complex deposition, infection, and mechanical injury in the form of diagnostic and therapeutic catheterization. Endothelial injury and the accumulation of platelet- and other cell-derived mediators promotes neointimal proliferation in an exaggerated wound-healing response, resulting in further anatomic narrowing of artery in the subsequent days and weeks. Future methods that may prove useful in protecting the individual with these vascular problems from acute myocardial infarction and its consequences are inhibition of multiple mediators of platelet aggregation and vasoconstriction, restoration of the presence of the normal endogenous inhibitors of platelet aggregation and vasoconstriction, and/or rapid therapeutic regeneration of the injured endothelium.
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PMID:Conversion from chronic to acute coronary heart disease syndromes. Role of platelets and platelet products. 778 65

A long-term study to identify age-dependent alterations in vascular reactivity in obese Zucker rats, a model for non-insulin-dependent diabetes mellitus, was carried out. On aortic rings of 12-week-old obese Zucker rats, but not in older animals (36 and 52 weeks), the following different effects in comparison to the lean rat control group were observed: (i) a significantly enhanced maximal relaxation to acetylcholine and A23187, which was abolished by the nitric oxide-synthase inhibitor L-nitro-arginine methyl ester (L-NAME); relaxation of aortic rings to the endothelium-independent vasodilator nitroglycerin was similar; (ii) more pronounced maximal 5-hydroxytryptamine-induced-contractions in the presence of L-NAME, and (iii) a more pronounced reduction in phenylephrine-induced contractions by verapamil. These results are suggestive of an altered calcium metabolism in the first weeks of development in the obese rat strain, which is probably responsible for the hypotension seen in this early time period.
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PMID:Age-related changes in vascular reactivity in genetically diabetic rats. 779 11

The endothelium influences local vascular tone by releasing endothelium-derived relaxing factors such as nitric oxide, prostacyclin and a putative hyperpolarizing factor. In isolated ophthalmic arteries and the perfused eye, all endothelial factors importantly contribute to vascular regulation. In larger ophthalmic vessels, this is due to their effects on vascular smooth muscle cells; in smaller vessels, pericytes can be influenced as well. Contracting factors formed include peptide endothelin-1 and cyclooxygenase products, such as thromboxane A2 and prostaglandin H2. In the peripheral circulation endothelial dysfunction occurs under pathological conditions, both in conduit arteries and the microcirculation. An imbalance of endothelium-derived relaxing and contracting factors could be important for the development of vascular ophthalmic complications like hypertension, diabetes, arteriolosclerosis and retinal ischemia. Endothelial dysfunction may also contribute to vasospastic events in retinal migraine and some forms of low tension glaucoma associated with Raynaud phenomenon and migraine.
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PMID:The vascular endothelium as a regulator of the ocular circulation: a new concept in ophthalmology? 780 Dec 20

A model of the pathogenesis of insulin-dependent diabetes mellitus, i.e. the initial phase of beta-cell destruction, is proposed: in a cascade-like fashion efficient antigen presentation, unbalanced cytokine, secretion and poor beta-cell defence result in beta-cell destruction by toxic free radicals (O2- and nitric oxide) produced by the beta cells themselves. This entire process is under polygenetic control.
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PMID:On the pathogenesis of IDDM. 782 44

A major surge of interest has recently focused upon nitric oxide (NO) as a mediator of autoimmune destruction of beta-cells in insulin-dependent diabetes mellitus (IDDM). It has been proposed that insulin producing cells in response to cytokines are induced to produce self destructing amounts of NO, and that endothelial cells or islet infiltrating macrophages may induce beta-cell death by releasing cytotoxic levels of NO within the islet. Recent findings in this field are presently discussed and we conclude that although NO might have a role in rodent IDDM, any putative role of NO in the pathogenesis of human IDDM remains to be clarified.
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PMID:Nitric oxide and pancreatic beta-cell destruction in insulin dependent diabetes mellitus: don't take NO for an answer. 785 14

During the past 8 years, it has become apparent that endothelium-dependent vascular relaxation is abnormal in a variety of disease states, including hypercholesterolemia, atherosclerosis, diabetes, hypertension, and following heart transplantation. Our laboratory and several others have examined dysfunctional regulation of vasomotor tone in hypercholesterolemia and atherosclerosis. These studies have led to the concepts that altered regulation of vasomotion by the endothelium (1) is an early development in atherosclerosis, (2) involves both large vessels (with overt atherosclerosis) and the microcirculation (in which atherosclerosis does not develop), and (3) can be reversed by lipid-lowering strategies. The mechanisms for the abnormalities underlying this form of endothelial dysfunction are likely multifactorial, but a major underlying factor appears to be increased oxidant degradation of endothelium-derived nitric oxide. In this review we examine the evidence supporting this conclusion and consider the implications of these findings.
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PMID:Physiologic consequences of increased vascular oxidant stresses in hypercholesterolemia and atherosclerosis: implications for impaired vasomotion. 786 77

The contribution of advanced glycation end-product (AGE) formation to alterations in nitrergic neurotransmission caused by 8-week streptozotocin-induced diabetes has been examined in the rat anococcygeus muscle. Relaxant responses to nitrergic nerve stimulation (0.5-5 Hz, 10-sec train), to nitric oxide (NO; 0.1-3 microM), to the NO donor, sodium nitroprusside (SNP; 5-500 nM), and to the cell-permeable analogue of cyclic guanosine monophosphate (cGMP), 8-bromo-cGMP (15 and 30 microM), were significantly smaller in muscles from diabetic rats than from control rats. Pretreatment with aminoguanidine hemisulphate (1 milligram drinking water) to inhibit AGE formation, did not alter the relaxant responses to nitrergic nerve stimulation, NO or SNP in tissues from control rats, or responses to NO or SNP in tissues from diabetic rats, however relaxations to nitrergic nerve stimulation were further reduced in tissues from diabetic rats. In anococcygeus muscles from untreated animals, a 20-min exposure to aminoguanidine (1 mM) in vitro had no effect on relaxations to nitrergic nerve stimulation. The results suggest that diabetes impairs nitrergic transmission in the rat anococcygeus at least partly through alterations in the cGMP-relaxation pathway. The impaired neurotransmission does not appear to be related to the formation of AGEs.
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PMID:Effect of aminoguanidine on the impaired nitric oxide-mediated neurotransmission in anococcygeus muscle from diabetic rats. 787 Feb 88

Accelerated atherosclerotic vascular disease is the leading cause of mortality in patients with diabetes mellitus. Endothelium-derived nitric oxide (NO) is a potent endogenous nitrovasodilator and plays a major role in modulation of vascular tone. Selective impairment of endothelium-dependent relaxation has been demonstrated in aortas of both nondiabetic animals exposed to elevated concentrations of glucose in vitro and insulin-dependent diabetic animals. The impaired NO release in experimentally induced diabetes may be prevented by a number of antioxidants. It has been hypothesized that oxygen-derived free radicals (OFR) generated during both glucose autoxidation and formation of advanced glycosylation end products may interfere with NO action and attenuate its vasodilatory activity. The oxidative injury may also be increased in diabetes mellitus because of a weakened defense due to reduced endogenous antioxidants (vitamin E, reduced glutathione [GSH]). A defective endothelium-dependent vascular relaxation has been found in animal models of hypertension and in hypertensive patients. An imbalance due to reduced production of NO or increased production of free radicals, mainly superoxide anion, may facilitate the development of an arterial functional spasm. Treatment with different antioxidants increases blood flow in the forearm and decreases blood pressure and viscosity in normal humans; vitamin E inhibits nonenzymatic glycosylation, oxidative stress, and red blood cell microviscosity in diabetic patients. Long-term randomized clinical trials of adequate size in secondary and primary prevention could support the free-radical hypothesis for diabetic diabetic vascular complications and the use of antioxidants to reduce the risk of coronary heart disease.
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PMID:Diabetes mellitus, hypertension, and cardiovascular disease: which role for oxidative stress? 788 82


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