Dilution acidosis: evidence for a role of intracellular pH in the control of ventilation.

Acute hyperosmolality results in an extracellular dilution acidosis and hypercarbia that does not stimulate ventilatory compensation. The osmotic stress is also associated with shifts in water and electrolyte balance and an increase in intracellular pH. The alkaline intracellular pH was hypothesized to have a role in preventing a normal respiratory response to the extracellular acidosis and hypercarbia. Therefore, this study examined the effect of ion-exchange blockade on intra- and extracellular pH and ventilation during acute hyperosmolality in the Pekin duck (Anas platyrhynchos) by using 31P-nuclear magnetic resonance spectroscopy. Both 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and amiloride inhibited the development of the intracellular alkalosis that normally develops in muscle during acute hyperosmolality. Instead, exposure to hyperosmotic stress during ion-exchange blockade resulted in a significant acidosis both intracellularly and extracellularly. Arterial pH decreased 0.10 +/- 0.04 pH unit with a sucrose infusion after either blocker, and intracellular pH decreased 0.11 +/- 0.06 and 0.16 +/- 0.04 pH units with a sucrose infusion after DIDS and amiloride, respectively. Ventilation increased 79 +/- 28 and 122 +/- 100%, respectively, during acute hyperosmolality after ion-exchange blockade with either DIDS or amiloride. The results suggest that intracellular pH may play a role in the ventilatory response to acid-base perturbations. The data also indicate that both Cl-/HCO3- and Na+/H+ exchanges are involved in the development of the intracellular alkalosis during hyperosmotically induced extracellular acidosis.