Summary of Discussions

Answering questions by N. Bank and F.H. Epstein, J.-P. Guignard stated that the increase in sodium excretion (?) with bicarbonate excretionfollowing clamping ofthe contralateral renal pedicle in dogs could not be ascribed to an increase in extracellular volume because, in his experiments, extracellular volume was kept constant by adapting the infusion rates to the urineflow observed in the precedingfew minutes. Compensatory adaptation of sodium and water excretion occurs, albeit to a small extent, even in non-expanded "non-diuretic" animals (G. Peters). In Guignard's experiments with NaHCO3 infused dogs, compensatory adaptation was not complete within 70 minutes after exclusion ofthe contralateral kidney, i.e., the excretion rates from the remaining kidney were not fully doubled (answer to N. Bank). The fact that renal denervation did not prevent compensatory adaptation, in dogs or in rabbits, shows that compensatory adaptation cannot be due to a kind of functional denervation of the remaining kidney andfurther suggests that denervation diuresis is due to a mechanism different from that responsible for adaptive diuresis (J.-P. Guignard to S. Carriere). Cardiac output, pulse rate and central venous pressure were not measured in Guignard's, Dirks' or Diezi's experiments. It was suggested by S. Bradley that circulatory changes could be more important in inducing compensatory adaptation than was apparentfrom the data presented, since primary changes of bloodpressure could be damped by a simultaneous fall of cardiac output. Answering a question by G. Giebisch, J.-P. Guignard stated that he observed no compensatory adaptation for hydrogen ion secretion after contralateral kidney exclusion in rabbits made acidotic by infusing ammonium chloride or acid phosphate: the remaining kidney was unable to further decrease urine pH or increase titratable acidity or ammonium excretion. Because an increase in the fractional excretion of bicarbonate in alkalotic animals is due to a decrease in tubular hydrogen ion secretion, it appears that hydrogen ion secretion may be decreased as part of the compensatory response when this is appropriate, but that it may not be increased above the levels reached in experimental metabolic acidosis. The possible role of prostaglandins in inducing compensatory adaptation after contralateral renal exclusion was discussed extensively, but no agreement was reached on possible conclusions. Data presented by J.H. Dirks and N.L.M. Wong suggest that prostaglandins may play a role in the depression oftheproximal tubular sodium reabsorption occurring immediately after contralateral clamping in dogs. This response was abolished in animals continuously infused with prostaglandins E2 or A2, but also in animals pretreated with indomethacin. Compensatory adaptation of the whole kidneyfractional excretion ofsodium, on the other hand, was abolished by the prostaglandins but only blunted by indomethacin. These observations could indicate that a release ofprostaglandins from either the clamped kidney or, more likely, from the remaining kidney, could play a role in inducing the adaptive diuresis, since compensatory adaptation of sodium excretion was prevented by presumably maximal prior stimulation ofprostaglandin receptors in the animals infused with prostaglandins, or by preventing prostaglandin synthesis with indomethacin. In contrast to thesefindings, J. Diezi stated that pretreatment of anesthetized rats with large doses of indomethacin did not interfere with compensatory adaptation. On the other hand, a possible role of prostaglandins in inducing compensatory adaptation does not appear to be directly tubular: J.H. Dirks and N.L.M. Wongfound that another vasodilator agent, acetylcholine, also abolished the