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

To investigate the influence of diabetes mellitus on vascular relaxation response, acetylcholine (ACh)-induced relaxation and production of cyclic GMP and cyclic AMP in aortic rings with endothelium were compared between alloxan-induced diabetic and control rabbits. ACh-induced relaxation was significantly attenuated in the aortic rings of diabetic rabbits. Concentration-response curve for ACh-induced relaxation in the aortic rings of control rabbits was shifted to the right by the pretreatment with hemoglobin, and this concentration-response curve was almost identical to that in the aorta from diabetic rabbits. Sodium nitroprusside (SNP)-induced relaxation in the aortic rings without endothelium from diabetic rabbits was similar to that in the aortic rings without endothelium from control rabbits. Basal levels of cyclic GMP and ACh-induced production of cyclic GMP were markedly lower in diabetic rabbits than those in control rabbits. On the other hand, there were no differences in basal and ACh-induced production of cyclic AMP between diabetic and control aorta. These results suggest that impairment of endothelium but not guanylate cyclase activity may be occurred in the aorta of diabetic rabbits. This impairment leads to the decrease in production of cyclic GMP through the attenuation of endothelium-derived relaxing factor (EDRF) release, and this may be responsible for the decreased endothelium-dependent relaxation of ACh.
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PMID:Decrease in endothelium-dependent relaxation and levels of cyclic nucleotides in aorta from rabbits with alloxan-induced diabetes. 216 Nov 18

The recent discovery of endothelium-derived relaxation factor (EDRF) has altered the traditional classification of vasodilators used in angina pectoris and heart failure. If a vasodilator induces release of EDRF from the epithelium it is classified as endothelium-dependent, if not it is independent. Sodium nitroprusside and SIN-1 (active metabolite of molsidomine) are the main independent vasodilators since the endothelium relaxation factor appears to be principally a nitric oxide radical in these synthetic vasodilators. In contrast, calcium-channel blockers and a good number of endogenous chemical mediators (acetylcholine, bradykinin, serotonin, etc.) are endothelium-dependent. Furthermore, simple increase in blood flow through the large vessels can result in endothelium-dependent vasodilation (flow rate-dependence) the extent of which depends on the drug examined. The fact that the pharmacologic response of a vasodilator can be altered under certain pathologic conditions (atherosclerosis, hypertension, diabetes, etc.) further increases the importance of the role of the vascular endothelium in the action of vasodilators since endothelial modulation may then be completely diverted to secretion of endothelium-derived contracting factors (EDCFS).
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PMID:[Vasodilator agents and the vascular endothelium]. 262 13

The intracellular content of cyclic GMP (cGMP) is known to mediate the effects of various vasodilating substances on glomerular mesangial cells. However, little is known about the role of soluble guanylate cyclase (SGC) in these cells in diabetes. We, therefore, investigated the changes in SGC activity as well as the cGMP content in rat mesangial cells (MC) cultured under high glucose or hypertonic conditions. The following results were obtained. 1. Sodium nitroprusside (SNP) (10(-4) M, 10min.) increased cyclic GMP (cGMP) content in MC from 8.17 +/- 0.99 pmol/mg protein to 981.6 +/- 86.3. 2. SNP (10(-4) M) stimulated SGC activity from 38.3 +/- 10.8 pmol cGMP formed/mg protein/10 minutes to 74.4 +/- 5.2. 3. In the coincubation experiment with bovine aortic endothelial cells, bradykinin (10(-6) M, 10min.) increased cGMP content in MC from 6.24 +/- 1.35 to 348.3 +/- 45.3. However, 4. the activity of SGC and SNP-induced increase of cGMP were not influenced by culturing MC in high glucose or hypertonic media. Similarly, the cGMP increase in MC coincubated with BAEC under bradykinin stimulation was not altered by culturing under high glucose or hypertonic conditions. These data suggested that SGC may play an important role in the regulation of cGMP content in MC. However, this enzyme may not be involved in the increase of cGMP content in MC cultured under high glucose condition.
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PMID:[Effect of glucose on soluble guanylate cyclase in cultured rat mesangial cells]. 810 Feb 85

Using a muscle bath technique the vascular response to KCl, noradrenaline, angiotensin II, acetylcholine, and sodium nitroprusside were evaluated in 13 patients with diabetes mellitus (DM group) and 15 nondiabetic (non-DM group) chronic renal failure patients treated with haemodialysis. There were no differences in age, duration of haemodialysis, blood pressure and the levels of plasma renin activity, noradrenaline, and parathyroid hormone between groups. After informed consent was obtained, a small piece of forearm vein was resected during the blood access surgery. The ring preparation of the blood vessel was sustained in the muscle bath filled with Krebs-Henseleit solution and the isometric tension development was recorded. All drugs produced concentration dependent responses in the ring preparations of both groups. Although there were no significant differences in Emax values for KCl- and angiotensin-II-induced contractions between groups, the value for noradrenaline in the DM group was significantly less than that in the non-DM group. Sodium nitroprusside completely relaxed the ring preparation precontracted by 10(-5) M noradrenaline. However, the response to acetylcholine in the DM group was significantly weaker than that in the non-DM group. These results suggest a reduced vascular response to noradrenaline and acetylcholine in dialysed diabetic renal failure patients, which may relate to the autonomic nervous system dysfunction.
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PMID:Vascular response to vasoactive agents in dialysed patients with chronic renal failure with and without diabetes mellitus. 817 67

Because diabetes is associated with impaired vascular endothelium, we have investigated endothelium-dependent cGMP stimulation in isolated glomeruli and renal vasodilation in normal and diabetes mellitus (DM) rats. Rats treated with streptozotocin (60 mg/kg iv) developed high blood glucose, polyuria, enlarged kidneys, and slow weight gain compared with control animals. Chronic treatment with insulin reversed these changes. In isolated glomeruli, the endothelium-dependent vasodilator, acetylcholine (ACh), stimulated cGMP accumulation concentration dependently; however, the response was significantly attenuated in glomeruli from DM rats when compared with normal rats or DM rats treated with insulin. Sodium nitroprusside-induced cGMP accumulation was also slightly but significantly reduced in glomeruli from DM rats, however, the response to atriopeptin III was unaltered. In rats, intravenous infusion of ACh (1 and 10 micrograms.kg-1.min-1) moderately decreased blood pressure and increased renal blood flow without a significant change in glomerular filtration rate. The renal vasodilatory response to ACh was significantly diminished in DM rats, but not in DM rats treated with insulin. Acute treatment with insulin did not restore the ACh response, although the blood glucose level was normalized. We conclude that there is a reduced renal vasodilatory response observed in DM, and this is due to an impairment of the renal vascular endothelium to produce endothelium-dependent relaxation factor (nitric oxide) and/or a defective soluble guanylate cyclase.
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PMID:Attenuated glomerular cGMP production and renal vasodilation in streptozotocin-induced diabetic rats. 838 64

Endothelium-dependent and endothelium-independent responses to exogenous vasoactive substances were compared in isolated, perfused mesenteric beds from control rats and in rats subjected to prolonged (15-17 weeks) streptozotocin induced diabetes. The main aim of the study was to determine whether the prolonged period of diabetes altered vascular endothelial function, and thereby modified vascular responsiveness to vasoconstrictors or vasodilators. Noradrenaline induced vasoconstriction was not significantly altered in preparations from diabetic rats compared to control. Vasodilator responses to acetylcholine (ACh) and ATP were endothelium-dependent, since they were greatly reduced or abolished after endothelium removal by perfusion with 0.1% Triton-X 100. The vasodilator action of these agents was fully preserved in the diabetic animals. Sodium nitroprusside produced a vasodilation which was endothelium-independent, this vasodilation was also preserved in the diabetic animal. We conclude that prolonged streptozotocin-induced diabetes does not reduce the ability of the mesenteric vascular endothelium to release vasodilator substances, nor does it alter the responsiveness of the bed to exogenous endothelium-independent vasodilator sodium nitroprusside or vasoconstrictor noradrenaline.
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PMID:Endothelium-dependent vasodilator responses of the isolated mesenteric bed are preserved in long-term streptozotocin diabetic rats. 845 94

Defective tissue perfusion and nitric oxide production and altered myo-inositol metabolism and protein kinase C activation have been invoked in the pathogenesis of diabetic complications including neuropathy. The precise cellular compartmentalization and mechanistic interrelationships of these abnormalities remain obscure, and nitric oxide possesses both neurotransmitter and vasodilator activity. Therefore the effects of ambient glucose and myo-inositol on nitric oxide-dependent cGMP production and protein kinase C activity were studied in SH-SY5Y human neuroblastoma cells, a cell culture model for peripheral cholinergic neurons. D-Glucose lowered cellular myo-inositol content, phosphatidylinositol synthesis, and phosphorylation of an endogenous protein kinase C substrate, and specifically reduced nitric oxide-dependent cGMP production a time- and dose-dependent manner with an apparent IC50 of approximately 30 mM. The near maximal decrease in cGMP induced by 50 mM D-glucose was corrected by the addition of protein kinase C agonists or 500 microM myo-inositol to the culture medium, and was reproduced by protein kinase C inhibition or downregulation, or by myo-inositol deficient medium. Sodium nitroprusside increased cGMP in a dose-dependent fashion, with low concentrations (1 microM) counteracting the effects of 50 mM D-glucose or protein kinase C inhibition. The demonstration that elevated D-glucose diminishes basal nitric oxide-dependent cGMP production by myo-inositol depletion and protein kinase C inhibition in peripheral cholinergic neurons provides a potential metabolic basis for impaired nitric oxide production, nerve blood flow, and nerve impulse conduction in diabetes.
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PMID:Modulation of basal nitric oxide-dependent cyclic-GMP production by ambient glucose, myo-inositol, and protein kinase C in SH-SY5Y human neuroblastoma cells. 860 30

1. We measured endothelium-dependent and independent dilatation of forearm resistance arteries in 29 men with diet-treated non-insulin-dependent diabetes mellitus and 18 age- and sex-matched control subjects. None of the diabetic patients had hypercholesterolaemia, overt hypertension or microproteinuria. 2. We examined endogenous and exogenous nitric oxide-mediated vasodilatation by measuring forearm blood flow with venous occlusive plethysmography after administration of acetylcholine (7.5 and 15 micrograms/min) and sodium nitroprusside (3 and 10 micrograms/min), respectively, into the brachial artery. NG-monomethyl-L-arginine was also infused to study the inhibition of basal and stimulated release of nitric oxide. 3. The vasodilatory response to acetylcholine, expressed as area under curve, was significantly decreased in the diabetic patients compared with the control subjects (P = 0.019). NG-monomethyl-L-arginine significantly reduced basal (P < 0.001) and acetylcholine-stimulated blood flow (P < 0.02) in both groups. The vasodilatory response (also expressed as area under curve) to sodium nitroprusside was significantly less (P = 0.044) in the diabetic patients than in the control subjects. 4. In the diabetic patients, impaired vasodilatory responses to acetylcholine were significantly correlated with higher serum triacylglycerols (P = 0.048) and lower high-density lipoprotein-cholesterol concentrations (P = 0.007); the association with high-density lipoprotein was independent of age, glycated haemoglobin and blood pressure. Sodium nitroprusside responses were not correlated with lipid and lipoprotein concentrations. 5. We conclude that there is impaired endothelial and smooth muscle cell function in men with diet-treated non-insulin-dependent diabetes mellitus uncomplicated by overt hypertension or microproteinuria. Endothelial dysfunction may be related to diabetic dyslipidaemia and associated metabolic disturbances.
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PMID:Impaired endothelium-dependent and independent dilatation of forearm resistance arteries in men with diet-treated non-insulin-dependent diabetes: role of dyslipidaemia. 894 95

Diabetes mellitus has profound adverse effects on vascular and, in particular, endothelial function. Although pressure-induced constriction ("myogenic tone") is a major contributor to the regulation of blood flow, little is known about the effects of diabetes on this response. Diabetes has been shown to diminish the dilation of cerebral arteries to synthetic ATP-sensitive K+ (KATP) channel openers. In this study, we explored the effects of diabetes induced in rats by streptozotocin on cerebral artery (250 to 300 microns) myogenic tone and on vasodilations to the synthetic KATP channel openers pinacidil and levcromakalim. Elevation of intravascular pressure caused a graded membrane potential depolarization and constriction, which was greater in arteries from diabetic rats compared with normal rats (at 60 mm Hg, 5 mV more depolarized and 22 microns more constricted). Pressurized arteries (at 60 mm Hg) from diabetic rats were 5- to 15-fold less sensitive to pinacidil and levcromakalim than were control arteries (EC50 values for pinacidil and levcromakalim were 1.4 and 0.6 mumol/L, respectively, in diabetic animals and 0.3 and 0.04, respectively, in control animals; P < .05). Removal of the endothelium or addition of a NO synthase inhibitor, NG-nitro-L-arginine (LNNA), in control arteries decreased the sensitivity to KATP channel openers and depolarized and constricted control arteries to levels similar to those observed in arteries from diabetic animals. Sodium nitroprusside caused a membrane potential hyperpolarization and enhanced the response to pinacidil in arteries from diabetic animals. Removal of the endothelium or LNNA had little effect on the apparent KATP channel opener sensitivity, the membrane potential, and pressure-induced constrictions of arteries from diabetic animals. The results are consistent with the hypothesis that this type of diabetes leads to a decrease in tonic NO release from the endothelium, which in turn causes membrane potential depolarization and vasoconstriction, resulting in a diminished response to KATP channel openers.
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PMID:Increased myogenic tone and diminished responsiveness to ATP-sensitive K+ channel openers in cerebral arteries from diabetic rats. 940 Mar 80

Several in vitro studies have suggested that nitric oxide may be the mediator of cytokine-induced beta-cell destruction. On the other hand, in vivo studies have given conflicting results: some studies suggesting that nitric oxide synthase inhibitors do not suppress streptozotocin-induced diabetes in mice, while others revealed that nitric oxide synthase inhibitors can reduce the incidence of insulin-dependent diabetes mellitus in rats. The results of the present study indicate that alloxan-induced diabetes in the male Wistar rats can be abrogated to a large extent by prior and simultaneous administration of the precursor of nitric oxide, L-arginine, where as NG-monomethy-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase, can completely block the beneficial action of L-arginine. Sodium nitroprusside, a nitric oxide donor, also showed significant inhibitory effect on the severity of diabetes induced by alloxan. Alloxan treatment reduced nitric oxide generation, whereas L-arginine and sodium nitroprusside, when given along with alloxan, enhanced nitric oxide production to control values. Induction of diabetes by alloxan in the experimental animals was associated with a marked elevation in plasma lactate, ketone body, and lipid peroxide levels with a simultaneous fall in plasma insulin and nitric oxide levels. Alloxan-induced diabetes also induced a fall in the levels of anti-oxidant enzymes such as superoxide dismutase, glutathione reductase, and total glutathione, and antioxidants: vitamin E and ceruloplasmin, and an increase in glutathione peroxidase and glutathione-S-transferase. All these biochemical abnormalities and antioxidant levels have improved to near normal levels in animals treated with insulin, L-arginine, and sodium nitroprusside. From the results of the present study, it is apparent that L-arginine and nitric oxide can prevent alloxan-induced beta-cell damage, and the development of diabetes, and restore the antioxidant status to near normal levels.
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PMID:Effect of L-arginine-nitric oxide system on chemical-induced diabetes mellitus. 982 40


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