SUMMARY1. The drinking of a variety of isotonic salt solutions provoked a short loaddependent diuretic response in man, similar in latency to that of a water diuresis and reaching its maximum 40-60 min from the start of drinking.2. Subjects differed in the threshold load at which the response became evident, and also in the magnitude of their responses.3. Changes in free water clearance matched the increases in urinary minute volume, with no significant change in either urinary sodium or potassium excretion.4. Changes in urinary pH and in ammonium excretion were similar to those described for a water diuresis.5. Drinking an isotonic solution of mannitol provoked a diuresis similar to that of the salt solutions. All subjects had diarrhoea after drinking the mannitol. Signals arising from the oropharynx might be partly responsible for eliciting the diuresis.6. The significantly smaller urinary responses to infusions of isotonic salt solutions directly into the stomach support this view.7. The absence of a significant response to 'sham drinking' appears inconsistent with this, but oropharyngeal signals may only have a priming role in man and interact with other signals to give the full response.

SUMMARY1. In a group of healthy humans, plasma vasopressin (AVP) levels fell on drinking either Tyrode or mannitol solutions isosmotic with plasma. Both the timing and magnitude of the fall were appropriate to account for the transient diuresis which followed the drinking.2. Although plasma expansion follows drinking Tyrode solution it occurred too late to account for the fall in plasma AVP. It was also too small to inhibit AVP secretion.3. Even though plasma volume tended to contract on drinking isosmotic mannitol solution a fall in plasma AVP and a diuresis occurred, similar to those found after drinking Tyrode solution.4. These findings appear to eliminate plasma volume expansion as the stimulus for the fall in plasma AVP and the associated diuresis on drinking isotonic fluids.5. In a further group of human subjects, bypassing the oropharynx by intragastric infusion resulted in a slower onset of diuresis after a water load.6. We suggest that receptors, as yet undefined, in the upper gastrointestinal tract contribute to the early stages of a water diuresis and account for the apparently inappropriate transient diuresis which follows the drinking of isotonic fluids.

The role of adenylate cyclase (AC) in the maintenance of the hydroosmotic response to serosal hypertonicity (SH) in anuran urinary bladder is disputed. In this study, norepinephrine (NE) significantly reversed the hydroosmotic response of Rana temporaria bladders in hypertonic medium (330 mosmol/kgH2O). The reversal was inhibited by yohimbine but was unaffected by prazosin and propranolol, indicating that NE action was mediated via alpha2-adrenergic receptors. Preincubation of bladders with indomethacin did not interfere with the inhibitory action of NE, contraindicating a role for prostaglandins. The SH hydroosmotic response was abolished in the presence of 5-n-ethyl-N-isopropyl amiloride (EIPA), but the antidiuretic hormone (ADH) hydroosmotic response was not. EIPA inhibits Na+/H+, known to be activated by cell shrinkage. An investigation of the anionic requirement of the SH hydroosmotic response revealed that replacement of bath Cl- with the nonpermeable anion gluconate reversibly abolished this response. In contrast, the hydroosmotic response to ADH was unaffected by Cl- removal; however, when Cl- was absent, it was no longer augmented in hypertonic bath. The SH response was inhibited by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)benzoate but not by the Na/K/2Cl inhibitor bumetanide. Our results show that not only the onset but also the maintenance of the SH hydroosmotic response is dependent on AC activity and does not differ in this respect to the ADH hydroosmotic response. The effect of modifying extracellular Cl- concentration, suggests that this anion, possibly functionally linked with Na+/H+ activity, may be involved in invoking the SH hydroosmotic response in anuran urinary bladder.

Research into the role of the gastrointestinal tract in the regulation of hydration has primarily concentrated on its function in the prevention of dehydration. The role of the gut in thirst, in the absorption of fluids and the consequences of diarrhoea are of importance in this respect. The function of the gut in the prevention of overhydration is less well understood. Intake of fluid increases excretion of water by the kidney. Inhibition of arginine vasopressin secretion, activation of renal nerves or hormonal release are possible effector mechanisms in this response.

1. This study aimed to shed light on the receptors involved in the diuretic response to drinking isotonic fluids in man by employing a polyethylene glycol-based bowel lavage solution (Golytely) which is reported to cause no net movement of fluid across the gut. 2. Drinking Golytely resulted in a transient hypotonic diuresis. Mean urine flow rose from control values of 0.9 ml min-1 to 10.1 ml min-1 70 min after the start of drinking. The increase in urine output was accompanied by a fall in urine osmolality from control values of 879 mosM kg-1 to 105 mosM kg-1. The diuresis is similar to that produced by ingestion of an equal volume of an absorbable electrolyte-based solution (Tyrode). 3. Neither solution produced changes in plasma osmolality or electrolytes, but Golytely provoked a 6.8% contraction of plasma volume, whereas drinking Tyrode resulted in plasma expansion. Copious diarrhoea was experienced by all subjects who drank Golytely solution and by none on drinking Tyrode solution. 4. The infusion of Golytely into the stomach resulted in a hypotonic diuresis similar in magnitude to that elicited by drinking. Drinking with simultaneous aspiration of gastric contents ('sham-drinking') did not produce a significant diuresis. 5. Plasma arginine vasopressin (AVP) levels did not fall following the drinking of Golytely. The assay used was sufficiently sensitive to measure changes of 0.6 pg AVP (ml plasma)-1. 6. The findings show that signals from the oropharynx do not mediate the diuretic response to drinking Golytely in man and that a mechanism other than inhibition of AVP release appears to be involved. The receptors mediating this response may lie in the stomach and/or small bowel since Golytely is not absorbed, as evidenced by the contraction of plasma volume and diarrhoea.