Dynamic arterial elastance measured by uncalibrated pulse contour analysis predicts arterial-pressure response to a decrease in norepinephrine.

BACKGROUND: Dynamic arterial elastance (Eadyn) has been proposed as an indicator of vascular tone that predicts the decrease in arterial pressure in response to changes in norepinephrine (NE). The purpose of this study was to determine whether Eadyn measured by uncalibrated pulse contour analysis (UPCA) can predict a decrease in arterial pressure when the NE dosage is decreased. METHODS: We conducted a prospective study in a university hospital intensive care unit. Patients with vasoplegic syndrome for whom the intensive care physician planned to decrease the NE dosage were included. Haemodynamic and UPCA (VolumeView and FloTrac; Edwards Lifesciences, Irvine, CA, USA) values were obtained before and after decreasing the NE dosage. Responders were defined by a >10% decrease in mean arterial pressure (MAP). RESULTS: Of 35 patients included, 11 (31%) were pressure responders with a median decrease of 13%. Eadyn was correlated to systolic arterial pressure (SAP) (r=0.255; P=0.033), diastolic arterial pressure (r=0.271; P=0.024), MAP (r=0.310; P=0.009), heart rate (r=0.543; P=0.0001), and transthoracic echography cardiac output (r=0.264; P=0.024). Baseline Eadyn was correlated with MAP changes (r=0.394; P=0.019) and SAP changes (r=0.431; P=0.009). Eadyn predicted the decrease in arterial pressure with an area under the receiver-operating-characteristic curve of 0.84 (95% confidence interval: 0.70-0.97). The best cut-off was 0.90. CONCLUSIONS: The present study confirms the ability of Eadyn measured by UPCA to predict an arterial pressure response to a decrease in NE. Eadyn may constitute an easy-to-use functional approach to arterial tone assessment regardless of the monitor used to measure its determinant. CLINICAL TRIAL REGISTRATION: DRCIT95.

Polarized expression of different monocarboxylate transporters in rat medullary thick limbs of Henle.

Extracellular lactic acid is a major fuel for the mammalian medullary thick ascending limb (MTAL), whereas under anoxic conditions, this nephron segment generates a large amount of lactic acid, which needs to be excreted. We therefore evaluated, at both the functional and molecular levels, the possible presence of monocarboxylate transporters in basolateral (BLMVs) and luminal (LMVs) membrane vesicles isolated from rat MTALs. Imposing an inward H(+) gradient induced the transient uphill accumulation of L-[(14)C]lactate in both types of vesicles. However, whereas the pH gradient-stimulated uptake of L-[(14)C]lactate in BLMVs was inhibited by anion transport blockers such as alpha-cyano-4-hydroxycinnamate, 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS), and furosemide, it was unaffected by these agents in LMVs, indicating the presence of a L-lactate/H(+) cotransporter in BLMVs, but not in LMVs. Under non-pH gradient conditions, however, the uptake of L-[(14)C]lactate in LMVs was transstimulated 100% by L-lactate, but by only 30% by D-lactate. Furthermore, this L-lactate self-exchange was markedly inhibited by alpha-cyano-4-hydroxycinnamate and DIDS and almost completely by 1 mM furosemide, findings consistent with the existence of a stereospecific carrier-mediated lactate transport system in LMVs. Using immunofluorescence confocal microscopy and immunoblotting, the monocarboxylate transporter (MCT)-2 isoform was shown to be specifically expressed on the basolateral domain of the rat MTAL, whereas the MCT1 isoform could not be detected in this nephron segment. This study thus demonstrates the presence of different monocarboxylate transporters in rat MTALs; the basolateral H(+)/L-lactate cotransporter (MCT2) and the luminal H(+)-independent organic anion exchanger are adapted to play distinct roles in the transport of monocarboxylates in MTALs.

Pathways for HCO-3 exit across the basolateral membrane in rat thick limbs.

We studied the pathways for HCO-3 transport in basolateral membrane vesicles (BLMV) purified from rat medullary thick ascending limbs (MTAL). An inward HCO-3 gradient in the presence of an inside-positive potential stimulated the rate of 22Na uptake minimally and did not induce a 22Na overshoot, arguing against the presence of electrogenic Na+-HCO-3 cotransport in these membranes. An inside-acid pH gradient stimulated to the same degree uptake of 86Rb+ (a K+ analog) with or without HCO-3. Conversely, applying an outward K+ gradient caused a modest intracellular pH (pHi) decrease of approximately 0.38 pH units/min, as monitored by quenching of carboxyfluorescein; its rate was unaffected by HCO-3, indicating the absence of appreciable K+-HCO-3 cotransport. On the other hand, imposing an inward Cl- gradient in the presence of HCO-3 caused a marked pHi decrease of approximately 1.68 pH units/min; its rate was inhibited by a stilbene derivative. Finally, we could not demonstrate the presence of a HCO-3/lactate exchanger in BLMV. In conclusion, the presence of significant Na+-, K+-, or lactate-linked HCO-3 transport could not be demonstrated. These and other data suggest that basolateral Cl-/HCO-3 exchange could be the major pathway for HCO-3 transport in the MTAL.

Functional and molecular characterization of luminal and basolateral Cl-/HCO-3 exchangers of rat thick limbs.

Cl-/HCO-3 exchange was measured in luminal (LMV) and basolateral (BLMV) membrane vesicles purified from rat medullary thick ascending limb (MTAL). Cl-/HCO-3 exchange in BLMV and LMV was inhibited by DIDS, with respective IC50 values of 3.2 +/- 0.9 and 15.2 +/- 5.2 microM, whereas Cl- conductances were DIDS insensitive. At constant external pH, BLMV 36Cl-/HCO-3 and 36Cl-/Cl- exchanges exhibited a sigmoidal pattern of activation as internal pH (pHi) increased from 6.1 to 8.0, whereas LMV 36Cl-/Cl- exchange was unchanged between pHi 6.7 and 7.8. The 165-kDa AE2 polypeptide and approximately 115-kDa AE1-related polypeptide were present only in BLMV. In contrast, AE1-related polypeptides of approximately 90 and 95 kDa were present not only in BLMV but also (in variable abundance) in LMV. We conclude that rat MTAL BLMV and LMV express distinct anion exchange activities and distinct sets of AE polypeptides. AE2 (and perhaps AE1) in BLMV likely contribute to HCO-3 absorption. In contrast, LMV exchangers may contribute to NaCl absorption via parallel coupling with the luminal Na+/H+ antiporters and/or may provide negative feedback regulation of HCO-3 absorption.

Water and solute permeabilities of medullary thick ascending limb apical and basolateral membranes.

The medullary thick ascending limb (MTAL) reabsorbs solute without water and concentrates NH4+ in the interstitium without a favorable pH gradient, activities which require low water and NH3 permeabilities. The contributions of different apical and basolateral membrane structures to these low permeabilities are unclear. We isolated highly purified apical and basolateral MTAL plasma membranes and measured, by stopped-flow fluorometry, their permeabilities to water, urea, glycerol, protons, and NH3. Osmotic water permeability at 20 degrees C averaged 9.4 +/- 0.8 x 10(-4) cm/s for apical and 11.9 +/- 0.5 x 10(-4) cm/s for basolateral membranes. NH3 permeabilities at 20 degrees C averaged 0.0023 +/- 0.00035 and 0.0035 +/- 0.00080 cm/s for apical and basolateral membranes, respectively. These values are consistent with those obtained in isolated perfused tubules and can account for known aspects of MTAL function in vivo. Because the apical and basolateral membrane unit permeabilities are similar, the ability of the apical membrane to function as the site of barrier function arises from its very small surface area when compared with the highly redundant basolateral membrane.

NH4+ as a substrate for apical and basolateral Na(+)-H+ exchangers of thick ascending limbs of rat kidney: evidence from isolated membranes.

1. We have used highly purified right-side-out luminal and basolateral membrane vesicles (LMVs and BLMVs) isolated from rat medullary thick ascending limb (MTAL) to study directly the possible roles of the LMV and BLMV Na(+)-H+ exchangers in the transport of NH4+. 2. Extravesicular NH4+ ((NH4+)o) inhibited outward H+ gradient-stimulated 22Na+ uptake in both types of vesicles. This inhibition could not be accounted for by alteration of intravesicular pH (pHi). 3. Conversely, in both plasma membrane preparations, the imposition of outward NH4+ gradients stimulated 22Na+ uptake at the acidic pHi (6.60) of MTAL cells, under conditions in which possible alterations in pHi were prevented. All NH4+ gradient-stimulated Na+ uptake was sensitive to 0.5 mM 5-(N,N-dimethyl)-amiloride. 4. The BLMV and LMV Na(+)-H+ exchangers had a similar apparent affinity for internal H+ (Hi+), with pK (-log of dissociation constant) values of 6.58 and 6.52, respectively. 5. These findings indicate that NH4+ interacts with the external and internal transport sites of the LMV and BLMV Na(+)-H+ antiporters, and that both of these exchangers can mediate the exchange of internal NH4+ ((NH4+)i) for external Na+ (Na+o) at the prevailing pHi of MTAL cells. 6. We conclude that operation of the BLMV Na(+)-H+ exchanger on the NH4(+)-Na+ mode may represent an important pathway for mediating the final step of NH4+ absorption, whereas transport of NH4+ on the apical antiporter may provide negative feedback regulation of NH4+ absorption.

Interactions of external and internal K+ with K(+)-HCO3- cotransporter of rat medullary thick ascending limb.

We studied [K+]i and [K+]o, where subscripts i and o refer to intracellular and extracellular, respectively, concentration dependency of the kinetic properties of the electroneutral K(+)-HCO3-cotransport, using suspensions of rat medullary thick ascending limb (mTAL). With the use of nigericin and monensin, [K+]i was clamped at various values, while maintaining [Na+]i = [Na+]o = 37 mM, [HCO3-]i = [HCO3-]o = 23 mM, and pHi = pHo = 7.4. As indicated by 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein HCO3(-)-dependent rates of change in pHi, at constant [K+]i, increasing the magnitude of the outward K+ gradient by varying [K+]o saturated HCO3-efflux with a Michaelis-Menten curve (apparent Michaelis constant for [K+]o = 2 mM, Hill coefficient = 1). On the other hand, increasing [K+]i from 30 to 140 mM, while either [K+]o or the magnitude of the K+ concentration gradient was fixed, saturated HCO3- efflux with a sigmoidal curve and yielded a Hill coefficient of 3.4 and 50% of maximum velocity at 70 mM [K+]i. These results indicate that [K+]i, independent of its role as a transportable substrate for the cotransport with HCO3-, has a role as an allosteric activator of the K(+)-HCO3- cotransporter. Such an allosteric modulation may contribute to the maintenance of net HCO3- absorption despite large in vivo physiological variations of K+ concentration in the medullary interstitium.

Control of H(+)-HCO3- plasma membrane transporters by urea hyperosmolality in rat medullary thick ascending limb.

Hyperosmolality inhibits bicarbonate absorption by the rat medullary thick ascending limb (MTAL) by unknown mechanisms. Intracellular pH (pHi) was monitored with use of 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein in rat MTAL tubule suspensions to specify the H(+)-HCO3- membrane transporters affected by hyperosmolality. Measurements were made after > or = 15-min incubation of the cells in media rendered hypertonic by urea to avoid any change in cell volume. Na(+)-H+ antiport activity, estimated from the Na(+)-induced initial rate of pHi recovery of Na(+)-depleted acidified cells in the presence of 0.1 mM furosemide to inhibit Na(+)-K(+)-2Cl- cotransport, was inhibited by 300 mM urea and 10(-8) M arginine vasopressin (AVP) in an additive manner. Na(+)-H+ antiport inhibition by urea hyperosmolality was maximal at 300 mM urea with a half-maximal inhibitory concentration of 75 mM and was due to a 28% decrease in maximum velocity (Vmax) with no effect on the Michaelis constant for sodium. Urea hyperosmolality (300 mM) did not affect steady-state intracellular calcium concentration ([Ca2+]i), assessed with use of fura 2 fluorescence, and still inhibited Na(+)-H+ antiport in MTAL cells loaded with 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid to minimize any transient change in [Ca2+]i during the preincubation in urea medium. Furthermore, 300 mM urea did not stimulate basal or AVP-induced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation. Plasma membrane H(+)-adenosinetriphosphatase (ATPase) activity and HCO3- transport, assessed by appropriate experimental protocols, were unaltered by 300 mM urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroneutral K+/HCO3- cotransport in cells of medullary thick ascending limb of rat kidney.

The renal medullary thick ascending limb (MTAL) of the rat absorbs bicarbonate through luminal H+ secretion and basolateral HCO3- transport into the peritubular space. To characterize HCO3- transport, intracellular pH (pHi) was monitored by use of the pH-sensitive fluorescent probe (2',7')-bis-(carboxyethyl)-(5,6)-carboxyfluorescein in fresh suspensions of rat MTAL tubules. When cells were preincubated in HCO3-/CO2-containing solutions and then abruptly diluted into HCO3-/CO2-free media, the pHi response was an initial alkalinization due to CO2 efflux, followed by an acidification (pHi recovery). The pHi recovery required intracellular HCO3-, was inhibited by 10(-4) M diisothiocyanostilbene-2-2'-disulphonic acid (DIDS), and was not dependent on Cl- or Na+. As assessed by use of the cell membrane potential-sensitive fluorescent probe 3,3'-dipropylthiadicarbocyanine, cell depolarization by abrupt Cl- removal from or addition of 2 mM barium into the external medium did not affect HCO3(-)-dependent pHi recovery, and the latter was not associated per se with any change in potential difference, which indicated that HCO3- transport was electroneutral. The HCO3(-)-dependent pHi recovery was inhibited by raising extracellular potassium concentration and by intracellular potassium depletion. Finally, as measured by use of a K(+)-selective extracellular electrode, a component of K+ efflux out of the cells was HCO3- dependent and DIDS sensitive. The results provide evidence for an electroneutral K+/HCO3- cotransport in rat MTAL cells.

Plasma membrane Na(+)-H+ antiporter and H(+)-ATPase in the medullary thick ascending limb of rat kidney.

To characterize H+ transport mechanisms in a fresh suspension of rat medullary thick ascending limb (MTAL) tubules, we have monitored intracellular pH (pHi) with use of the fluorescent probe 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein. First, a Na(+)-H+ antiporter was identified in bicarbonate-free N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered media at 25 degrees C. pHi recovery of Na-depleted acidified cells was dependent on extracellular sodium concentration, which was inhibited by amiloride in a manner consistent with simple competitive interaction with one external transport site (amiloride Ki = 1.5-2.1 x 10(-5) M); Na-induced pHi recovery of acidified cells was electroneutral since it was not affected by 5 or 100 mM extracellular potassium in the presence or absence of valinomycin. Second, at 37 degrees C, pHi recovery after acute intracellular acidification caused by 40 mM acetate addition to cell suspension was inhibited 36% by 200-400 nM bafilomycin A1, a macrolide antibiotic that specifically inhibits vacuolar-type H(+)-ATPase at submicromolar concentrations. In addition, amiloride-insensitive pHi recovery was inhibited by bafilomycin A1, 10(-3) M N-ethylmaleimide, and 10(-4) M preactivated omeprazole but not by 10(-5) M vanadate, 10(-4) M SCH 28080, or removal of extracellular potassium. Also, metabolic inhibition by absence of substrate, 10(-4) M KCN, or 5 x 10(-4) M iodoacetic acid inhibited amiloride-insensitive pHi recovery. The inhibitory effects of absence of metabolic substrate and iodoacetic acid were removed by reexposure to glucose and L-leucine and by exogenous ATP, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of H+/HCO3- transport in the medullary thick ascending limb of rat kidney.

The rat MTAL secretes protons into the tubular fluid and thus absorbs bicarbonate at substantial rates. Yet the cellular mechanisms of H+/HCO3- transport in the rat MTAL remain largely unsettled. We have performed intracellular pH recovery studies with use of the fluorescent probe BCECF in suspensions of rat MTAL fragments. Luminal H+ secretion occurs by two mechanisms (each responsible for 50% of the normal pHi recovery rate): (1) an electroneutral Na+/H+ antiporter that has an Na-Km of about 11 mM and is inhibited by amiloride (Ki = 2.8 x 10(-5) M); (2) a primary H+ pump that is inhibited by 10(-4) M NEM and 10(-4) M omeprazole, but not by 10(-4) M vanadate or removal of external K. These results suggest the presence of a vacuolar H(+)-ATPase rather than a H(+)-K(+)-ATPase. Basolateral HCO3 exit occurs predominantly by a Cl(-)- and Na(+)-independent electroneutral K+/HCO3- symporter, that has an HCO3-Km of about 17 mM, and is partially inhibited by 10(-4) M DIDS. Basolateral HCO3- efflux was not accompanied by variations of membrane potential monitored with the Em-sensitive fluorescent probe DIS-C3-5, and was not affected by maneuvers that depolarize the cells. It was strongly inhibited by cellular K depletion and dependent on transmembrane K gradient. We conclude that the rat MTAL should secrete protons through both Na+/H+ antiporter and H(+)-ATPase, and that basolateral HCO3- exit should occur through an electroneutral K+/HCO3- symporter.

[Hyponatremia of acute pulmonary infections]. / Hyponatrémie des pneumopathies infectieuses aiguës.

The mechanism of hyponatremia associated with pneumonia has been debated. In particular, the responsibility of inappropriate antidiuretic hormone secretion has been questioned. We have shown that inappropriate antidiuretic hormone secretion is a nearly constant finding during pneumonia and is roughly proportional to the extent of pneumonia. Nevertheless, it must be emphasized that extracellular fluid volume may be increased, diminished or normal during pneumonia, depending on the underlying condition (congestive heart failure, cirrhosis) or on the importance of extrarenal losses (sweats, fever). Careful clinical and laboratory assessment of extracellular fluid volume should enable adequate therapy.

Does the stress of admission to an intensive care unit influence arginine vasopressin secretion and renal diluting ability?

The pathogenesis of excessive arginine vasopressin (AVP) release and hyponatraemia in euvolaemic intensive care unit (ICU) patients is poorly understood. Stress has frequently been proposed as a possible determinant, but its actual responsibility has not been adequately assessed. Therefore, water-load tests were prospectively performed in 11 patients admitted to the ICU for severe or potentially severe diseases, but who had no other condition which could result in excessive AVP release or impairment of renal diluting ability. Renal diluting ability was normal in 9 patients. Two patients exhibited very slight defects, which might be the consequence of subclinical haemodynamic alterations, since one had a pulmonary embolism and the other manifested a gastrointestinal haemorrhage just after the completion of the water load. Nevertheless, plasma AVP levels decreased in response to the water load in all the patients, resulting in a significant decrease in mean values. Plasma norepinephrine values were found to be elevated both before and after water loading. A highly significant correlation existed between the levels of norepinephrine and those of AVP measured before the load, but was lost after it. In addition, norepinephrine values were markedly elevated in two patients who exhibited strictly normal renal diluting abilities, and no correlation was found between plasma norepinephrine values and any parameter of renal water excretion. Our study shows that the stress of a serious illness and of admission to an ICU does not seem to interfere, by itself, with osmotic regulation of AVP secretion and renal diluting ability, and that sympathetic activation is not, under such circumstances, a predominant stimulus for AVP release.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of glucagon on H(+)-HCO3- transport in Henle's loop, distal tubule, and collecting ducts in the rat.

Paired micropuncture experiments were carried out in somatostatin-infused volume-expanded rats to examine the effects of a glucagon infusion (0.05 ng.min-1.g body wt-1) on urinary acidification and tubular handling of bicarbonate. Whole kidney and single-nephron glomerular filtration rate were not affected by glucagon. In thyroparathyroidectomized (TPTX) rats, glucagon inhibited the reabsorption of total CO2 in Henle's loop. In intact animals, however, the latter effect was not observed. In the distal tubule accessible to micropuncture, net total CO2 absorption was observed during volume expansion plus somatostatin infusion, which reversed to net total CO2 secretion during glucagon infusion in Wistar rats; thus the late distal delivery of total CO2 increased almost 80%. Marked inhibition of urinary acidification occurred in all animals as evidenced by a rise in urine pH and bicarbonate excretion. Conversely, a somatostatin infusion, which decreased the plasma glucagon concentration, stimulated net total CO2 absorption along the distal tubule and augmented final urine acidification in Wistar rats. Finally, urine-minus-blood PCO2 during alkaline diuresis was significantly reduced by glucagon infusion in bicarbonate-loaded TPTX rats. We conclude that 1) glucagon inhibits bicarbonate absorption in superficial Henle's loop in TPTX but not in intact rats, and 2) glucagon stimulates bicarbonate secretion and/or inhibits proton secretion in the distal tubule and collecting ducts, which leads to reduced urinary acidification.

Acute infectious pneumonia is accompanied by a latent vasopressin-dependent impairment of renal water excretion.

The mechanism of hyponatremia associated with pneumonia has not been definitely established. Moreover, renal water excretion was never systematically investigated in cases of pneumonia without hyponatremia. We therefore studied nine consecutive patients breathing spontaneously (nasal oxygen in five), with acute infectious pneumonia and normal plasma sodium concentration. All the patients were previously healthy. Water loads were administered during illness and after recovery. Extracellular fluid volume, arterial blood pressure, PaO2, and PaCO2 were identical during and after pneumonia. By contrast, renal water excretion was markedly impaired during pneumonia and returned to normal values after recovery. This was attested to by a significant decrease in minimum urine osmolality together with significant increases in the percentage of the excreted water load and the maximum free water clearance, after resolution of the pneumonia. Plasma arginine vasopressin values were significantly higher during pneumonia than after recovery despite similar plasma sodium concentrations, both before and after water load. A positive correlation between plasma arginine vasopressin and minimum urine osmolality was found during pneumonia. Thus, impairment in renal water excretion appeared to be due to resetting of the vasopressin osmostat and could not be attributed to any recognized nonosmotic stimulus for vasopressin secretion. On the other hand, these defects varied in severity depending on the extent of the pneumonia and persisted until clearing of alveolar opacities, accounting for their protracted course in some patients. We conclude that water excretion is impaired in most if not in all patients with acute infectious pneumonia (especially if extended), and that the administration of hypotonic solutions should be avoided in these patients.

Glucagon inhibits urinary acidification in the rat.

The effects on urinary acidification of an acute infusion of glucagon (GLU) were studied by paired experiments in plasma-replete rats whose endogenous GLU secretion was restrained by a 0.7 ng.min-1.g body wt-1 somatostatin infusion. GLU did not affect the glomerular filtration rate in any of the plasma-replete rats studied. In 10 thyroparathyroidectomized (TPTX) rats and five intact rats subjected to hypotonic volume expansion, a low-dose (0.02 ng.min-1.g body wt-1) GLU infusion that raised the plasma GLU concentration from 302 +/- 63 to 1,010 +/- 140 pg/ml significantly increased the urinary bicarbonate excretion and decreased the urinary net acid excretion; a high-dose (0.05 ng.min-1.g body wt-1) glucagon infusion in the intact rats, that increased the plasma GLU concentration to 1,609 +/- 307 pg/ml, further enhanced the urinary bicarbonate excretion rate. In intact plasma-replete rats that were not subjected to a hypotonic volume expansion, low- and high-dose GLU infusions failed to affect the urinary bicarbonate excretion rate. Finally, no change in urinary excretion rates was noted in TPTX volume-expanded time control rats. We conclude that 1) physiological increments in plasma GLU concentration decrease urinary acidification by affecting the tubular H+/bicarbonate transport; 2) the bicarbonaturic effect of GLU may be blunted by the renal effects of high circulating antidiuretic hormone levels, or may be facilitated in an undetermined manner by hypotonic volume expansion.

Effects of antidiuretic hormone on urinary acidification and on tubular handling of bicarbonate in the rat.

Paired micropuncture experiments were carried out in plasma-replete volume-expanded rats to examine the acute effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on urinary acidification and tubular handling of bicarbonate and chloride. No effect was detected on the fractional absorption of water, total CO2, and chloride at end-proximal and early distal sites of superficial nephrons in intact animals; dDAVP, however, inhibited the fractional absorption of total CO2 in Henle's loop while stimulating that of chloride in thyroparathyroidectomized (TPTX) somatostatin-infused rats. In the distal tubule accessible to micropuncture, net total CO2 secretion was observed during hypotonic volume expansion, which reversed to net total CO2 absorption during dDAVP infusion in intact Wistar rats. Marked stimulation of urinary acidification occurred in all animals as attested by a fall in urine pH and bicarbonate excretion. Net acid excretion almost doubled in intact rats. We conclude that (a) antidiuretic hormone (ADH) inhibits fractional bicarbonate absorption in the thick ascending limb while stimulating that of chloride at least in TPTX somatostatin-infused rats, and (b) ADH stimulates proton secretion (or inhibits bicarbonate secretion) in the distal tubule and cortical collecting ducts, which leads to enhanced urinary acidification.