Background-Water drinking increases blood pressure profoundly in patients with autonomic failure and substantially in older control subjects. The mechanism that mediates this response is not known. Methods and Results-We studied the effect of drinking tap water on seated blood pressure in 47 patients with severe autonomic failure (28 multiple system atrophy [MSA], 19 pure autonomic failure patients [PAF]). Eleven older controls and 8 young controls served as control group. We also studied the mechanisms that could increase blood pressure with water drinking. Systolic blood pressure increased profoundly with water drinking, reaching a maximum of 33Ϯ5 mm Hg in MSA and 37Ϯ7 in PAF mm Hg after 30 to 35 minutes. The pressor response was greater in patients with more retained sympathetic function and was almost completely abolished by trimethaphan infusion. Systolic blood pressure increased by 11Ϯ2.4 mm Hg in elderly but not in young controls. Plasma norepinephrine increased in both groups. Plasma renin activity, vasopressin, and blood volume did not change in any group. Conclusions-Water drinking significantly and rapidly raises sympathetic activity. Indeed, it raises plasma norepinephrine as much as such classic sympathetic stimuli as caffeine and nicotine. This effect profoundly increases blood pressure in autonomic failure patients, and this effect can be exploited to improve symptoms due to orthostatic hypotension. Water drinking also acutely raises blood pressure in older normal subjects. The pressor effect of oral water is an important yet unrecognized confounding factor in clinical studies of pressor agents and antihypertensive medications.

During the sympathetic activation induced by tilt, a similar oscillatory pattern based on an increased LF rhythmicity characterized the spontaneous variability of neural sympathetic discharge, R-R interval, and arterial pressure.

The neuropathic postural tachycardia syndrome results from partial sympathetic denervation, especially in the legs.

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The aim of this study was to determine the role of increased plasma cortisol levels in the pathogenesis of hypoglycemiaassociated autonomic failure. Experiments were carried out on 16 lean, healthy, overnight fasted male subjects. One group ( n ϭ 8) underwent two separate, 2-d randomized experiments separated by at least 2 mo. On day 1 insulin was infused at a rate of 1.5 mU/kg per min and 2 h clamped hypoglycemia (53 Ϯ 2 mg/dl) or euglycemia (93 Ϯ 3 mg/dl) was obtained during morning and afternoon. The next morning subjects underwent a 2-h hyperinsulinemic (1.5 mU/kg per min) hypoglycemic (53 Ϯ 2 mg/dl) clamp study. In the other group ( n ϭ 8), day 1 consisted of morning and afternoon 2-h clamped hyperinsulinemic euglycemia with cortisol infused to stimulate levels of plasma cortisol occurring during clamped hypoglycemia (53 mg/dl). The next morning (day 2) subjects underwent a 2-h hyperinsulinemic hypoglycemic clamp identical to the first group. Despite equivalent day 2 plasma glucose and insulin levels, steady state epinephrine, norepinephrine, pancreatic polypeptide, glucagon, ACTH and muscle sympathetic nerve activity (MSNA) values were significantly ( P Ͻ 0.01) blunted after day 1 cortisol infusion compared to antecedent euglycemia. Compared to day 1 cortisol, antecedent hypoglycemia produced similar blunted day 2 responses of epinephrine, norepinephrine, pancreatic polypeptide and MSNA compared to day 1 cortisol. Antecedent hypoglycemia, however, produced a more pronounced blunting of plasma glucagon, ACTH, and hepatic glucose production compared to day 1 cortisol. We conclude that in healthy overnight fasted men ( a ) antecedent physiologic increases of plasma cortisol can significantly blunt epinephrine, norepinephrine, glucagon, and MSNA responses to subsequent hypoglycemia and ( b ) these data suggest that increased plasma cortisol is the mechanism responsible for antecedent hypoglycemia causing hypoglycemia associated autonomic failure. ( J. Clin. Invest. 1996. 98:680-691.)