| مستخلص: |
A profound defect in dorsal foot skin perfusion in response to heating in type 2 diabetic individuals has been observed. In prior studies, we have determined that most of this defect correlates with insulin resistance, may be related to the integrity of small unmyelinated C-fiber nerves, is likely not mediated by nitric oxide (NO), and is at least partially correctible with regular exercise training. Thus, the purpose of this study was to examine the acute effects of blockage of local prostaglandin and NO release and exercise status on stimulated skin perfusion in type 2 diabetes. In 28 controls (15 sedentary, 13 exercisers) and 25 diabetic (16 sedentary, 9 diabetic) subjects, a small dose of L-NAME (0.54 g), a nitric oxide synthase inhibitor, dissolved in normal saline was administered into the dermis of right foot using a small microdialysis catheter for a period of 100 minutes, with normal saline alone going into the left foot. One hour prior to administration of L-NAME, a single, adult dose (325 mg) of generic aspirin (ASA) was taken orally. Concurrent laser Doppler skin blood flow measurements of perfusion in response to ASA plus L-NAME (L-NAME trial) or ASA with saline placebo (ASA), both basally at 32oC and with heating to 40oC (10 min) and 44oC (50 min), were made. In both conditions of maximally stimulated skin perfusion (44°C), the effect of diabetes itself was not significant in our subjects (p=0.12 for L-NAME, p=0.20 for ASA). Grouping subjects by exercise status alone (exercisers, EX, n=30; sedentary, SED, n=22), heated skin perfusion in EX subjects was 54.06 ± 9.09 (arbitrary perfusion units) with L-NAME and 82.93 ± 10.41 in ASA trials, which was significantly depressed compared to SED subjects with perfusions of 89.62 ± 13.24 and 113.96 ± 9.21, respectively (p<0.01). ASA alone depressed stimulated perfusion significantly more in EX than SED (p<0.05). In EX only, L-NAME further decreased heated perfusion compared with ASA alone (p<0.05). There were no significant differences in perfusion at 32 or 40°C. Our results suggest that with exercise status may be even more important than the presence of type 2 diabetes with regard to ASA suppression of local prostaglandin synthesis and skin perfusion, although defective release of EDHF cannot be ruled out by these observations. Thus, for all individuals, regular aerobic exercise appears to be critical to maintenance of normal prostaglandin release in the foot dorsum. ADA-Funded Research [ABSTRACT FROM AUTHOR] |
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