Insulin-dependent diabetes mellitus (IDDM) is associated with abnormal function of the vascular endothelium and it is proposed that this defect could underlie many of the associated vasculopathies [1]. Studies from our laboratory and others have reported impaired vasodilatory responses to the endothelium-dependent vasodilator acetylcholine (ACh) in isolated arteries from diabetic subjects [2] and in mesenteric [3], femoral [4] and aortic [5] arteries from the streptozotocin (STZ)-diabetic rat (an animal model of uncontrolled IDDM). Although a physiological endothelium-dependent dilatory role of ACh has sometimes been questioned, the reduced relaxation of arteries from diabetic animals to other endothelium-dependent dilators [1] and to increasing luminal flow [6] would suggest that the poor ACh responses reflect a generalised endothelial defect. The abnormal ACh response is likely to result from either decreased nitric oxide (NO) synthesis or increased NO degradation [3,4]. Several mechanisms have been hypothesised, among which is the suggestion that oxidative stress could play an important role [7,8]. Diabetologia (1998) Summary Impaired endothelium-dependent relaxation could underlie many of the vascular complications associated with insulin-dependent diabetes mellitus, and may be mediated by increased oxidative stress. The effect of antioxidants on vascular endothelial function and oxidative stress of streptozotocin-diabetic rats was assessed by dietary supplementation with vitamins E and C. Diabetic (i. v. streptozotocin, 45 mg/kg) male Sprague-Dawley rats were fed one of six supplemented diets containing 75.9, 250, or 500 mg vitamin E/kg chow, 250 mg vitamin C/kg H 2 0, 250 mg vitamin E/kg chow plus 250 mg vitamin C/kg H 2 O, or chow deficient in vitamin E, and then compared to standard-fed control rats. After 4 weeks, small mesenteric arteries were dissected and mounted on a small vessel myograph, concentration response curves were then constructed to noradrenaline, acetylcholine and sodium nitroprusside. Acetylcholinemediated relaxation was impaired in arteries from diabetic rats (pEC 50 6.701 ± SEM 0.120, n = 8) compared to controls (7.386 ± 0.078, n = 6; p < 0.05). The 500 mg/kg vitamin E diet further impaired maximum relaxation to acetylcholine (58.2 ± 10.5 vitamin E, n = 7 vs 84.4 ± 5.3 % standard, p < 0.05), and the combined vitamin E plus C diet impaired maximum relaxation to sodium nitroprusside (48.5 ± 4.1 in vitamin E + C, n = 8 vs 75.6 ± 3.9 % standard; p < 0.01). However, plasma 8-epi-prostaglandin (PG)F 2 a (measured as an estimate of oxidative stress) was dose-dependently decreased in rats on vitamin E supplemented diets. Dietary antioxidant supplementation did not reverse impaired endothelial function in this model of uncontrolled diabetes despite a concomitant decrease in oxidative stress. [Diabetologia (1998) 41: 148±156]
Objective To determine whether corticotrophin releasing hormone plays a role in the regulation of tone Setting A teaching hospital research laboratory.Sample Thirty-seven women undergoing elective nonlabour caesarean section under regional anaesthesia.Methods Human corticotrophin releasing hormone (1, 10, 100 nmoyL) was added to strips of term, nonlabouring myometrium mounted in an organ bath, and the effect on spontaneous, oxytocin (1 nmol/L) or prostaglandin FZa (100 nmovL) stimulated contractions determined. Cyclic adenosine monophosphate (CAMP) content of the tissue was also determined by enzyme immunoassay.Results Corticotrophin releasing hormone did not affect myometrial tension development in any of the experimental protocols. cAMP increased transiently after addition of corticotrophin releasing hormone (166.7 .c 12.7% at 1 minute) but this was not reflected by any change in tension.Conclusions This study suggests that despite high maternal plasma concentrations of corticotrophin releasing hormone in pregnancy at term, this peptide is unlikely to play a direct role in the control of myometrial contractility in nonlabouring myometrium.in tern nonlabouring human myometrium.
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