Dopamine [beta]-hydroxylation in diabetes and diabetic autonomic neuropathy

Dopamine [beta]-hydroxylase (DBH) has been studied in healthy subjects and diabetic patients, some of whom had autonomic neuropathy. DBH was assayed by a recently described in vivo tritium release method (10,11). Dopamine specifically labeled in the [beta] position, [[beta]-3H]DA, was given intravenously, and the time course of tritiated water (THO) release into the total body water was measure as an index of DBH activity in sympathetic neurons. We simultaneously assayed [3H]norepinephrine metabolite excretion.The DBH activity of patients with autonomic neuropathy as a group did not differ significantly from that of diabetics without neuropathy or healthy controls. Our data do not support the suggestion (7) that a deficit in DBH activity is responsible for sympathetic neuronal dysfunction in diabetic autonomic neuropathy. This syndrome thus differs from idiopathic orthostatic hypotension in which condition there is an impairment in the ability of sympathetic neurons to hydroxylate dopamine (9).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24287/1/0000553.pd

The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society Decreased Prorenin Processing Develops before Autonomic Dysfunction in Type 1 Diabetes*

It is well documented that diabetic patients with chronic complications have decreased renin secretion and elevations in the renin precursor prorenin. It is uncertain, however, whether the abnormal processing of prorenin is reflective of microvascular disease, hypertension, or autonomic neuropathy. Dechaux et al. (Transplant Proc. 18:1598–1599, 1986) observed abnormalities in prorenin processing in uncomplicated diabetes and suggested that it was the result of subclinical autonomic neuropathy. To test this hypothesis, we measured renin, prorenin, and autonomic function in early type 1 diabetes at a time when there is little or no microvascular disease or hypervolemia. Thirty-seven patients (10 males, 27 females) enrolled 2–22 months after diagnosis in a longitudinal study in which renin, prorenin, and autonomic function were measured annually for 3 years. Forty-one age-matched control subjects were also studied

Local infusion of ascorbate augments NO-dependent cutaneous vasodilatation during intense exercise in the heat

Nitric oxide (NO)-dependent cutaneous vasodilatation is reportedly diminished during exercise performed at a high (700W) relative to moderate (400W) rate of metabolic heat production. The present study evaluated whether this impairment results from increased oxidative stress associated with an accumuluation of reactive oxygen species (ROS) during high intensity exercise. On two separate days, 11 young (mean +/- SD, 24 +/- 4years) males cycled in the heat (35 degrees C) at a moderate (500W) or high (700W) rate of metabolic heat production. Each session included two 30min exercise bouts followed by 20 and 40min of recovery, respectively. Cutaneous vascular conductance (CVC) was monitored at four forearm skin sites continuously perfused via intradermal microdialysis with: (1) lactated Ringer solution (Control); (2) 10mm ascorbate (Ascorbate); (3) 10mm l-NAME; or (4) 10mm ascorbate+10mm l-NAME (Ascorbate+l-NAME). At the end of each 500W exercise bout, CVC was attenuated with l-NAME (approximate to 35% CVCmax) and Ascorbate+l-NAME (approximate to 43% CVCmax) compared to Control (approximate to 60% CVCmax; allP0.87). Conversely, CVC was elevated with Ascorbate (approximate to 72% CVCmax; both P0.05) at the end of both 700W exercise bouts. We conclude that oxidative stress associated with an accumulation of ascorbate-sensitive ROS impairs NO-dependent cutaneous vasodilatation during intense exercise