We conclude that atrial natriuretic peptide can induce a gradual decrease in blood pressure, sometimes followed by symptomatic hypotension, which occurs suddenly. This phenomenon depends on the duration of the infusion as well as the dose. Moreover, the dose effect is enhanced during low sodium intake. This warrants careful observation of patients with essential hypertension who are given infusions of atrial natriuretic peptide over longer periods. The effect ofdesmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure CHRISTOPHER J MATHIAS, PAUL FOSBRAEY, DAVID F DA COSTA, ANDREW THORNLEY, ROGER BANNISTER Abstract Day and night urine volume, morning and evening body weight, and supine and sitting blood pressure were measured in five patients with chronic autonomic failure who were not receiving treatment with drugs. AU had nocturnal polyuria, overnight weight loss, and a pronounced postural fall in blood pressure, with lowest levels in the morning. Desmopressin (24 ,ug given intramuscularly at 8 pm) reduced nocturnal polyuria, diminished overnight weight loss, raised supine blood pressure, and reduced the postural fail, especially in the morning, when patients were often at their worst.

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1. To investigate whether carbohydrate contributes to postprandial hypotension in autonomic failure, the cardiovascular, biochemical and hormonal effects of oral glucose and an iso-osmotic solution of oral xylose were studied on separate occasions in six patients with chronic autonomic failure. The effects of oral glucose were also studied in eight normal subjects. 2. In the patients oral glucose lowered blood pressure substantially (-34 +/- 7% at 60 min, area under curve -24.9 +/- 3.5%, P less than 0.001) and for a prolonged period (-25 +/- 4% at 120 min). Plasma noradrenaline levels did not change. In the normal subjects blood pressure was unchanged and plasma noradrenaline rose, suggesting a compensatory increase in sympathetic nervous activity. 3. In the patients xylose caused a smaller and more transient fall in blood pressure (-15 +/- 6% at 90 min, area under curve -8.9 +/- 4%, P less than 0.05) with a non-significant elevation in packed cell volume (36.7 +/- 1.8 to 38.2 +/- 1.8). It was therefore unclear if xylose was exerting osmotic effects within the bowel which contributed to the small blood pressure fall. Packed cell volume did not change in either the patients or normal subjects after glucose. 4. In the patients and normal subjects plasma insulin rose after glucose. Insulin levels were unchanged after xylose. Levels of pancreatic polypeptide and neurotensin, a potential vasodilator, rose in the patients only. The latter rose to a similar extent after both glucose and xylose, making it unlikely that neurotensin alone accounted for the hypotension. 5. These studies indicate that the carbohydrate components of a meal, and in particular those causing insulin release, contribute to postprandial hypotension in patients with autonomic failure.

The effects of the organophosphate acetylcholinesterase (AChE) inhibitor soman (31.2 micrograms/kg s.c.) on guinea-pig brain AChE, transmitter, and metabolite levels were investigated. Concentrations of acetylcholine (ACh) and choline (Ch), noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites, and six putative amino acid transmitters were determined concurrently in six brain regions. The brain AChE activity was maximally inhibited by 90%. The ACh content was elevated in most brain areas by 15 min, remaining at this level throughout the study. This increase reached statistical significance in the cortex, hippocampus, and striatum. The Ch level was significantly elevated in most areas by 60-120 min. In all regions, levels of NA were reduced, and levels of DA were maintained, but those of its metabolites increased. 5-HT levels were unchanged, but those of its metabolites showed a small increase. Changes in levels of amino acids were restricted to those areas where ACh levels were significantly raised: Aspartate levels fell, whereas gamma-aminobutyric acid levels rose. These findings are consistent with an initial increase in ACh content, resulting in secondary changes in DA and 5-HT turnover and release of NA and excitatory and inhibitory amino acid transmitters. This study can be used as a basis to investigate the effect of toxic agents and their treatments on the different transmitter systems.

The haemodynamic responses to intravenous insulin (0-15 units/ kg) were measured in five patients with chronic autonomic failure who were not receiving drug treatment. After the administration of insulin supine blood pressure fell steadily, with a substantial reduction even before the onset of hypoglycaemia. None of the patients showed the usual range of neuroglycopenic symptoms, but they all became drowsy, with increasing sedation as the blood glucose concentration fell. In four other patients with autonomic dysfunction intravenous injection of 25-50 ml of 50% glucose alone caused a striking, although transient, fall in blood pressure. Hypoglycaemia was reversed by a 10 minute intravenous infusion of 100 ml of25% glucose; this did not lower blood pressure further and rapidly restored previous levels ofalertness.Consideration must be given to the hypotensive potential of insulin in patients with autonomic failure during an insulin stress test. The inability of these patients to show the usual manifestations ofhypoglycaemia, plus the short lived, though pronounced, reduction in blood pressure after intravenous administration of 50% glucose, may further increase the risks of this procedure.