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

Four patients with idiopathic orthostatic hypotension (I.O.H.) and one with postural hypotension and diabetes were studied. Plasma-renin activity (P.R.A.) was low and did not rise appropriately with salt restriction and diuretic stimulation. Aldosterone levels were normal and rose with diuretic therapy. Plasma-volume, plasma dopamine beta-hydroxylase, urinary catecholamines, metanephrines, and vanillyl mandelic acid (V.M.A) were normal. Treatment with indomethacin (75-150 mg/day) raised the upright blood-pressure (B.P.) by an average of 20-30 mm Hg diastolic and allowed the four patients with I.O.H. to walk about without orthostatic symptoms but it had no effect in the fifth patient. When indomethacin was discontinued in one patient who had been taking it for 9 months with symptomatic relief, the B.P. fell to pretreatment levels within 48 h. When indomethacin was reinstituted the B.P. rose again. Indomethacin was more effective in these patients than either propranolol or fludrocortisone. There may be an absolute or relative excess of certain vasodepressor prostaglandins in the peripheral vessels which results in pooling of blood and orthostatic hypotension. If this is the case indomethacin might improve the orthostatic symptoms of I.O.H. by its inhibitory effect on prostaglandin synthesis, but its mechanism of action remains to be determined.
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PMID:Treatment of idiopathic orthostatic hypotension (Shy-Drager syndrome) with indomethacin. 7 34

The influence of diclofenac sodium (Voltaren) on glucose metabolism was investigated in a group of 13 maturity onset diabetics treated by a standard diet alone. A second group of 14 patients with maturity onset diabetes well controlled by a standard diet and tolbutamide (Rastinon) was examined for a possible drug interaction. Determinations of capillary blood glucose as well as assessments of urine sugar by Clinitest and 24-hour urine glucose determinations were regularly done before and during treatment with diclofenac sodium. The results of this study show no alteration of glucose metabolism. These laboratory data suggest that there is no clinically relevant interaction between diclofenac sodium and tolbutamide. Neither the blood glucose profiles of the individual patients nor those of the two above-mentioned groups showed any alterations of blood glucose concentration. Diclofenac sodium, a non-steroidal antirheumatic drug, may be recommended in the treatment of rheumatic diseases in diabetics. Indomethacin, naproxen, sulindac, diftalon and diclofenac are more recently developed antirheumatic drugs which have been specially tested in diabetics.
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PMID:[The effect of diclofenac sodium on the metabolism of diabetics in qualitative diet therapy with an without tolbuamide. A clinically oriented study in aged diabetics with rheumatic disease]. 30 47

In diabetic animals, reduced endoneurial perfusion and oxygen content have been linked to neuropathic abnormalities and might be amenable to pharmacological manipulation. In streptozotocin-induced diabetic rats, we studied the influence of guanethidine adrenergic sympathectomy, indomethacin treatment and a combined strategy on: serial in vivo motor and sensory conduction, resistance to ischemic conduction failure, in vitro myelinated and unmyelinated conduction, endoneurial perfusion and endoneurial oxygen tension. Unlike previous work diabetic animals had normal endoneurial perfusion but lower endoneurial oxygen tensions after six months of hyperglycemia. Guanethidine worsened sensory conduction despite lower microvascular resistance and an improvement in endoneurial oxygen tension. In contrast, indomethacin improved motor and sensory conduction but not oxygen tension. These studies do not support a linkage between conduction deficits and early endoneurial microangiopathy in experimental diabetes. Indomethacin, or related agents may offer a new therapeutic approach toward diabetic neuropathy through a mechanism independent of the endoneurial microvasculature.
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PMID:The influence of indomethacin and guanethidine on experimental streptozotocin diabetic neuropathy. 142 41

The relative contribution of atrial natriuretic peptide (ANP) and vasodilatory prostaglandins to hyperfiltration in Wistar rats with experimental diabetes was studied 6-8 wk after streptozocin injection. Plasma levels of immunoreactive ANP were significantly higher (P less than 0.01) in hyperglycemic diabetic (72.9 +/- 11.7 pg/ml) than in normoglycemic diabetic (44.8 +/- 8.6 pg/ml) or nondiabetic (40.0 +/- 6.8 pg/ml) rats. Blocking endogenous ANP by specific ANP-antiserum infusion reduced significantly (P less than 0.01) glomerular filtration rate (GFR) and renal plasma flow (RPF) of hyperglycemic rats compared with preinfusion values (1.23 +/- 0.06-1.02 +/- 0.04; 2.87 +/- 0.25-2.40 +/- 0.10 ml.min-1.100 g-1, respectively). However, correction of hyperfiltration and hyperperfusion was only partial (nondiabetic rats GFR 0.85 +/- 0.07; RPF 2.27 +/- 0.13 ml.min-1.100 g-1). Because diabetic rats with hyperglycemia also had an increased urinary excretion of prostacyclin metabolite 6-keto-prostaglandin F1 alpha (220.6 +/- 62.8 ng/24 h) compared with nondiabetic rats (51.2 +/- 2.7 ng/24 h), we wondered whether excessive prostacyclin formation contributed to hyperfiltration and hyperperfusion in this setting. Indomethacin infusion partially reduced GFR (1.25 +/- 0.07 to 1.06 +/- 0.07 ml.min-1.100 g-1, P less than 0.05) and RPF (2.85 +/- 0.11 to 2.46 +/- 0.12 ml.min-1.100 g-1, P less than 0.01) in diabetic rats. The combined infusion of ANP antiserum and indomethacin normalized GFR and RPF in diabetic rats with hyperglycemia (1.27 +/- 0.05 to 0.88 +/- 0.05 and 2.84 +/- 0.10 to 2.22 +/- 0.06 ml.min-1.100 g-1, respectively; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Apr
PMID:Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperperfusion of diabetic rats. 153 57

1. This study investigated the responsiveness to vasoconstrictor agents (including endothelin-1, ET-1) of aortic rings from rats with two-week streptozotocin (STZ, 60 mg kg-1, i.v.)-induced diabetes and vehicle-treated control rats. The basal tension was 10 g, which was estimated to be more physiological than the tension of 1-2 g that has been previously used for most studies of aortic rings from diabetic rats. 2. Maximum responses to ET-1 (0.13-18 nM), KCl (2-20 mM) or CaCl2 (10 microM-10 mM) were reduced in aortae from STZ-treated rats compared to those from control rats. Such reductions were still evident after removal of the endothelium. 3. Responses to noradrenaline (NA, 0.1 nM-26 microM) of aortae from STZ-treated rats were not significantly different from responses of aortae of control rats. 4. Removal of endothelium resulted in a significant reduction in the EC50 values for NA of rings from both STZ-treated rats (6.90 +/- 0.13 and 8.17 +/- 0.35 (-log M) with and without endothelium, respectively, n = 5) and control rats (6.90 +/- 0.15 and 8.37 +/- 0.44 (-log M) with and without endothelium, respectively, n = 5). 5. In calcium-free medium (with 1 mM EGTA), responses to NA and ET-1 were reduced compared with those in normal Krebs solution and maximum responses were less in rings from STZ-treated compared with control rats. 6. Indomethacin (5 microM) did not prevent the reduced maximum responsiveness to ET-1 in rings from STZ-treated rats compared with those from controls.7. This study indicates that changes in vascular responsiveness to ET-1, KCI and CaCl2 (but not NA) occur in aortae of two-week STZ-treated rats. The endothelium does not appear to play a major role in mediating changes in responsiveness to ET-1.
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PMID:Attenuated responses to endothelin-1, KCl and CaCl2, but not noradrenaline, of aortae from rats with streptozotocin-induced diabetes mellitus. 181 Jun 3

The goal of this study was to determine the mechanism of impaired responses of cerebral arterioles during diabetes mellitus. To induce diabetes, rats were injected with streptozotocin. Rats were characterized as diabetic by a blood glucose of greater than 300 mg/dl. Diameter of pial arterioles was measured with intravital microscopy in nondiabetic and diabetic rats during superfusion with acetylcholine (ACh), ADP, the thromboxane (Tx) analogue U-46619, and nitroglycerin. ACh increased pial arteriolar diameter in nondiabetic rats and did not alter diameter in diameter in diabetic rats. ADP increased pial arteriolar diameter in nondiabetic rats and produced minimal changes in diameter of arterioles in diabetic rats. Tx analogue U-46619 produced similar constriction of cerebral arterioles in nondiabetic and diabetic rats. In addition, nitroglycerin produced similar dilatation of cerebral arterioles in nondiabetic and diabetic rats, suggesting that impaired dilatation of cerebral arterioles in diabetic rats was not related to nonspecific impairment of vasodilatation. Next, we examined the possibility that impaired responses of cerebral arterioles in diabetic rats in response to ACh and ADP may be related to production of a cyclooxygenase constrictor substance. Indomethacin and the TxA2-prostaglandin (PG) H2 receptor antagonist SQ 29548 restored dilator responses to ACh and ADP in diabetic rats toward that observed in nondiabetic rats. Indomethacin and SQ 29548 did not alter responses in nondiabetic rats. Thus diabetes mellitus impairs endothelium-dependent responses of cerebral arterioles. The mechanism of impaired responses of cerebral arterioles during diabetes mellitus appears to be related to the production of a cyclooxygenase constrictor substance and presumably related to stimulation of the TxA2-PGH2 receptor.
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PMID:Mechanism of impaired responses of cerebral arterioles during diabetes mellitus. 182 54

A possible relationship between protein kinase C activation and impaired receptor-mediated endothelium-dependent relaxation in diabetes mellitus was examined in isolated aorta from normal rabbit exposed to elevated glucose. Aorta treated for 10 min with 4-phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, showed decreased relaxations to the endothelium-dependent vasodilator, acetylcholine, similar to normal aorta exposed to elevated glucose (22 and 44 mM) for 6 h. Relaxations to the receptor-independent endothelium-dependent vasodilator, A23187, and those caused by the direct smooth muscle vasodilator, sodium nitroprusside, were unaffected by treatment with PMA or exposure to elevated glucose. Indomethacin increased relaxations to acetylcholine of aorta treated with PMA indicating a role for vasoconstrictor prostanoids. PMA caused a significant increase in basal and acetylcholine-stimulated release of vasoconstrictor prostanoids including thromboxane A2 from aortic segments with, but not without endothelium. Protein kinase C inhibitors, H-7 or sphingosine, restored the abnormal acetylcholine-induced relaxations as well as suppressed the abnormal release of prostanoids in aorta exposed to elevated glucose. These findings suggest that the dysfunction of receptor-mediated endothelium-dependent relaxation associated with exposure to elevated glucose is due to increased production of vasoconstrictor prostanoids by the endothelium as a consequence of protein kinase C activation.
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PMID:Elevated glucose impairs endothelium-dependent relaxation by activating protein kinase C. 202 34

The majority of cases of impotence are associated with vascular risk factors such as diabetes, hypercholesterolemia, hypertension and smoking. These factors induce impairment of endothelium-dependent relaxation of blood vessels in man and in experimental animals. In this study the effects of hypercholesterolemia on the reactivity of rabbit corpus cavernosum smooth muscle strips to endothelium-dependent and endothelium-independent agents were investigated. New Zealand White rabbits (n = 14) were randomly divided into control and treatment groups. The control group (n = 7) received a regular diet while the treatment group (n = 7) was fed a diet of 0.5% cholesterol and 4% peanut oil for 10 weeks. Animals were then sacrificed and the corporal tissue studied in organ chambers for isometric tension measurement. Tissue was contracted with phenylephrine and concentration-dependent relaxation to acetylcholine, in the presence and absence of indomethacin, and to nitroprusside were examined. Blood level of cholesterol in the cholesterol-fed group was significantly higher compared to the control group. Contractions to phenylephrine were similar in both groups. Hypercholesterolemia, however, inhibited relaxation to acetylcholine but did not alter relaxation to nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent, direct smooth muscle dilator. Indomethacin enhanced the relaxations to acetylcholine in both control and cholesterol-fed groups but did not correct the difference in the relaxation to acetylcholine between both groups. It is concluded that hypercholesterolemia impairs endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. The mechanism for the endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the cGMP-dependent relaxation of corporal smooth muscle. Impairment of endothelium-dependent relaxation of corporal smooth muscle may contribute to the pathophysiology of impotence associated with hypercholesterolemia in man.
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PMID:Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. 205 97

We here report a case of Bartter's syndrome occurring in association with diabetes mellitus. The patient, an insulin-dependent diabetic, presented with hypokalaemia, inappropriate kaliuresis and metabolic alkalosis. He had high plasma renin activity, relatively low plasma aldosterone, and resistance to infused angiotensin II. A high potassium diet raised total body potassium and serum potassium, did not affect plasma renin activity, but raised plasma aldosterone significantly and did not alter the resistance to angiotensin II. Indomethacin administered acutely reduced urinary potassium and kallikrein excretion and, on chronic administration, lowered plasma renin activity, urinary chloride excretion, and raised serum potassium. Salt restriction resulted in a prompt and significant reduction in urinary sodium and chloride excretion. Urinary kallikrein excretion was very high throughout, increased with sodium restriction, and decreased with sodium loading. Oral potassium supplementation partially corrected the hypokalaemia, but did not affect blood sugar control. In this patient the primary defect appears to have been primary urinary potassium wasting, rather than sodium or chloride wasting. The striking effects of indomethacin suggest that prostaglandins may play a fundamental role in the genesis of the syndrome.
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PMID:Bartter's syndrome and diabetes mellitus. 225 25

The contribution of peripheral arterial tissue to the development of vascular changes in Diabetes Mellitus (DM) was studied using the perfused tail artery from rats treated with Streptozotocin (25 mg/kg ip for 5 days). Dose-response curves to KCl and phenylephrine (PE) were constructed; the response to PE was significantly higher in DM than control arteries. No difference was found in the response to KCl between DM and controls. The response to vasodilators Acetylcholine (Ach), Papaverine, PAF-Acether were independent of the type of vasoconstrictor used to increase the vascular tone (KCl or PE). The response in the diabetic was significantly smaller than in the control arteries. The infusion of Indomethacin had no effect on the vasodilator response but enhanced the response to PE. The mechanical removal of endothelium increased the response to PE; presumably the vasoconstriction elicited by PE is counterbalanced by the release of vasodilators such as PGI2 and EDRF of endothelium origin. Infusion of Methylene Blue, that inhibits intracellular accumulation of c-GMP, in DM and control preparations partially blocked papaverine response and totally abolished the response to Ach and PAF-Acether. These data support an active participation of the peripheral arterial wall to the pathological changes present in diabetes mellitus.
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PMID:Contribution of the arterial tissue to vascular pathology in diabetes mellitus. 237 18


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