Increased Na/H antiporter and Na/3HCO3 symporter activities in chronic hyperfiltration. A model of cell hypertrophy.

Abstract

A B S T R AC T The effect of chronic hyperfiltration, a model of cell hypertrophy, on H/HCO~ transporters was examined in the in vivo microperfused rat proximal tubule. Hyperfiltradon was induced by uninephrectomy with subsequent increased dietary protein. After 2 wk the hyperfiltration group had a higher glomerular filtration rate (2.21 -+ 0.13 vs. 1.48 -0.12 ml/min), associated with increased kidney weight (1.71 -+ 0.05 vs. 1.23 -+ 0.04 g). HCO 3 absorptive rate measured in tubules perfused with an ultrafiltrate-like solution (25 mM HCOs) was higher in the hyperfiltration group (183 -17 vs. 100 _+ 16 pmol/mm per min). The activities of the apical membrane Na/H antiporter and basolateral membrane NaJ3HCO 3 symporter were assayed using the measurement of cell pH [(2'7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein] in the doubly microperfused tubule in the absence of contact with native fluids. After 2 wk of hyperfiltration Na/H antiporter activity, assayed as the effect of luminal Na removal on cell pH, was increased 114%. Basolateral membrane NaJ3HCO3 symporter activity, assayed as the effect of a decrease in peritubular [HCO3] (25 to 5 mM) or in peritubular [Na] (147 to 25 mM) in the absence of luminal and peritubular chloride, was increased 77 and 113%, respectively, in the hyperfiltration group. Steady-state cell pH, measured with physiologic, ultrafiltrate-like luminal and peritubular perfusates, was significantly higher in the hyperfiltration group (7.27 -0.02 vs. 7.14 _+ 0.03). In similar studies, performed 24 h after uninephrectomy and protein feeding, kidney weight was increased 10%, Na/H antiporter activity 39%, and Na/3HCO~ symporter activity 46%. At this time cell pH was not different between the two groups. The results demonstrate that chronic hyperfiltration is associated with parallel increases in Na/H antiporter and Na/3HCO s symporter activities. If a decrease in cell pH is the signal that triggers these adaptations, it occurs early, and the adaptations can be maintained in the absence of sustained cell acidification.Address reprint requests to Dr. Patricia

Prenatal programming of rat proximal tubule Na+/H+ exchanger by dexamethasone

“…In addition, the increase in proximal tubule volume absorption and Na ϩ /H ϩ exchanger activity could be secondary to an increase in single nephron GFR, because we have shown that GFR does not change and yet there is a reduction in nephron number in adult rats that are administered prenatal dexamethasone (35,36), and not a primary event potentially causing hypertension. Previous studies showing an increase in proximal tubule transport or Na ϩ /H ϩ exchanger have used uninephrectomy with or without protein loading, which likely resulted in a greater increase in single nephron GFR than in the current study (37,38). In addition, hypertension has been noted by prenatal administration of dexamethasone in the absence of a reduction in nephron number (36).…”

Mineralocorticoid modulation of apical and basolateral membrane H+/OH-/HCO3- transport processes in the rabbit inner stripe of outer medullary collecting duct.

“…Parallel modulation of apical and basolateral membrane H+/OH-/HCO transporters in response to a variety of conditions has been extensively documented in the proximal tubule. Parallel adaptive increases in apical membrane Na+/H+ antiporter activity and basolateral membrane Na+/3HCO5 cotransporter activity have been found under the chronic conditions of metabolic acidosis (35,36) and alkalosis (35), respiratory acidosis (37,38) and alkalosis (37), hyperfiltration (39), and K+ depletion (40). In addition, acute exposure of the in vitro microperfused proximal tubule to angiotensin II has been found to increase in parallel the activities of these two transporters (41 ).…”

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

“…In addition, the PTs from the remnant kidney adapt (2 wk after surgery) by doubling the functional expression of both apical Na-H exchange and basolateral Na/HCO 3 cotransport (758). 50 This adaptation does not appear to be an acute effect of acidosis inasmuch as blood pH was not different from that of control rats (758). Whether this upregulation of NBCe1 activity is accompanied by an increase in the abundance of NBCe1 transcripts and/or protein is not documented in this study.…”