Cisternal Na+ transport inhibition and the ventilatory response to CO2.
When PCO2 rises transiently, glia or neurons may move ions across their cell membranes to restore intracellular pH, in the process changing extracellular pH. Inhibiting ion transport would result in a different extracellular fluid pH (a putative stimulus for the medullary chemoreceptors) and, therefore, in an altered ventilation in response to PCO2. We infused two ion transport inhibitors, amiloride and bumetanide, into the cisterna magna of anesthetized rabbits and compared their ventilatory response to a rebreathing maneuver with sham rabbits receiving no inhibitor. Amiloride (10(-5)-10(-3) M) had no effect; 3 h of 10(-2) M amiloride increased the frequency of breathing and decreased tidal volume but had no net effect on minute ventilation. Bumetanide (10(-3) M) had no effect after 1 h of infusion, but by 3 h it had decreased tidal volume and minute ventilation at 6 and 7% end-tidal CO2 fraction, respectively, during the rebreathe. Three hours of infusion of amiloride and bumetanide did not affect ventilation in a manner consistent with our predictions from previous studies of ionic changes in cerebrospinal fluid. During the 1st h, when neuronal and glial ion transport in the ventrolateral medulla should be inhibited, we found no effect of ion transport inhibition. We conclude that, during the transient hypercapnia of a rebreathing maneuver, Na+/H+ exchange and Na(+)-K(+)-2Cl- cotransport do not play a significant role in immediate rapid pH homeostasis by cellular ion transport in the microenvironment of the medullary chemoreceptors.
Sullivan
M P
MP
University of Virginia, Charlottesville 22908.
Adams
J M
JM
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology*; D002946:Cisterna Magna / Q000378:metabolism*; D007267:Injections; D008168:Lung / Q000473:pathology; D008297:Male; D011817:Rabbits; D012119:Respiration / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*
D002034:Bumetanide; D002245:Carbon Dioxide; D000584:Amiloride; D012964:Sodium