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H R Jacobson

Publications and source records attributed to H R Jacobson.

At least 73 records · Page 4Linked to original sources
PubMed1986

Regulation of net bicarbonate transport in rabbit cortical collecting tubule by peritubular pH, carbon dioxide tension, and bicarbonate concentration.

The effects of changes in peritubular pH, carbon dioxide tension (PCO2), and HCO3- concentration on net HCO3- transport was examined in in vitro perfused cortical collecting tubules (CCTs) from unpretreated New Zealand white rabbits. Lowering peritubular HCO3- concentration and pH by reciprocal replacement of HCO3- with Cl-, significantly stimulated net HCO3- absorption. Lowering peritubular HCO3- concentration and pH, by substitution of HCO3- with gluconate, while keeping Cl- concentration constant, also stimulated net HCO3- absorption. Raising peritubular HCO3- concentration and pH, by reciprocal replacement of Cl- with HCO3-, inhibited net HCO3- absorption (or stimulated net HCO3- secretion). When the tubule was cooled, raising peritubular HCO3- concentration had no effect on net HCO3- transport, suggesting these results are not due to the passive flux of HCO3- down its concentration gradient. The effect of changes in ambient PCO2 on net HCO3- transport were also studied. Increasing the ambient PCO2 from 40 mmHg to either 80 or 120 mmHg, allowing pH to fall, had no effect on net HCO3- transport. Similarly, lowering ambient PCO2 to 14 mmHg had no effect on net HCO3- transport. Simultaneously increasing peritubular HCO3- concentration and PCO2, without accompanying changes in peritubular pH, i.e., isohydric changes, stimulated net HCO3- secretion to the same degree as nonisohydric increases in peritubular HCO3- concentration. Likewise, isohydric lowering of peritubular HCO3- concentration and PCO2 stimulated net HCO3- absorption. We conclude that: acute changes in peritubular HCO3- concentration regulate acidification in the CCT and these effects are mediated by a transcellular process; acute changes in ambient PCO2 within the physiologic range have no effect on HCO3- transport in the in vitro perfused CCT; and acute in vitro regulation of CCT acidification is independent of peritubular pH.

Absorption↗
PubMed1986

Hormonal regulation of proton secretion in rabbit medullary collecting duct.

With the exception of aldosterone, little is known about the hormonal regulation of distal nephron acidification. These experiments investigated the effects of prostaglandin E2, indomethacin, lysyl-bradykinin, 8-bromo-cyclic AMP, and forskolin on proton secretion in the major acidifying segment of the distal nephron, the medullary collecting duct from inner stripe of outer medulla. Using in vitro microperfusion and microcalorimetry, net bicarbonate reabsorption (proton secretion) was measured in rabbit medullary collecting ducts before, during, and after exposure to each test substance. PGE2 reduced proton secretion 12.2%, while the following substances stimulated proton secretion: indomethacin 14.2%; 8-bromo-cyclic AMP 34.5%; forskolin 39%. Lysyl-bradykinin was without effect. These studies demonstrate that distal nephron acidification, in addition to being stimulated by aldosterone, is significantly inhibited by the hormone PGE2. The stimulation of proton secretion by cAMP suggests that other hormones known to activate adenylate cyclase may also influence distal nephron acidification.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Effects of in vitro aldosterone on the rabbit cortical collecting tubule.

Considerable evidence indicates that the cortical collecting tubule is a target epithelium for aldosterone. Isolated perfused cortical collecting tubules from rabbits given large doses of deoxycorticosterone acetate (DOCA) for several days, or whose endogenous production of aldosterone is increased by dietary means, exhibit large lumen-negative transepithelial voltages, increased sodium (Na) absorption, and increased potassium (K) secretion compared with tubules from normal animals. However, controversy exists regarding the response of this nephron segment to acute in vitro administration of aldosterone. To address this issue we performed three groups of experiments: 1) clearance experiments on adrenalectomized rabbits to determine the minimum time required after in vivo aldosterone administration before significant changes in sodium excretion are observed; 2) microperfusion experiments on cortical collecting tubules from normal and adrenalectomized rabbits in which transepithelial voltage was measured before and after adding aldosterone to the bath; 3) microperfusion experiments on cortical collecting tubules from adrenalectomized rabbits in which transepithelial voltage, sodium and potassium flux were measured before and after in vitro exposure to aldosterone or dexamethasone. The clearance studies demonstrate that after a 2 hr latent period aldosterone produces significant antinatriuresis without change in K excretion. In vitro studies failed to reveal a steroid-induced change in the transepithelial voltage of cortical collecting tubules from either normal or adrenalectomized rabbits. However, aldosterone added in vitro to collecting tubules from adrenalectomized rabbits produced an increase in net Na absorption without a significant change in voltage or K secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1985

Na to Cl permeability in newborn rabbit superficial and juxtamedullary proximal convoluted tubules.

It has been previously demonstrated that superficial (SF) versus juxtamedullary (JM) proximal convoluted tubules (PCT) of rabbit have different intrinsic transport characteristics: Na is less permeable than Cl in the latter portions of the SFPCT, while Cl is less permeable than Na throughout the JMPCT. These permeability differences have major influences on the mechanism of salt reabsorption across the proximal tubules. However, both populations of PCT have the same embryological origin. Studies therefore were designed to examine whether two distinct populations of PCT exist at birth or whether a second population of tubules develops with delivery as a result of some unidentified acute change in humoral factor affecting epithelial transport properties. Both morphological and electrophysiological studies were conducted on PCTs from rabbits within 36 h of birth. Both transmission and scanning electron microscopy studies clearly disclosed that SFPCT are less mature than the JMPCT. Also the SFPCT had a lower Na permeability than Cl (0.55 +/- 0.06) while the JMPCT had a higher Na permeability than Cl (1.37 +/- 0.11). Thus these studies demonstrate that intrinsic heterogeneity of PCT is present at birth. Since the SF Na to Cl permeability approximates that of free diffusion these studies suggest that epithelial discrimination in PCT is part of a maturation process.

Animals↗
PubMed1984

Hydrogen ion permeability of the rabbit proximal convoluted tubule.

Acidification of luminal fluid in the proximal convoluted tubule has been modeled as a pump-leak system. Using isolated perfused rabbit proximal convoluted tubules in a HCO-3/CO2-free in vitro environment, we studied "H+ leak" by imposing pH gradients across the tubule and measuring the change in pH from perfusate to collected fluid. Active acidification was inhibited by acetazolamide with and without hypothermia. At 21 degrees C a symmetrical H+ leak with an apparent permeability coefficient of approximately 0.15 cm X s-1 was found with either a lumen-to-bath or bath-to-lumen [H+] gradient. At 37 degrees C a much higher apparent permeability coefficient was found that was dependent on luminal lactate. Phosphate movement did not affect H+ fluxes significantly. Without luminal lactate, the apparent permeability coefficient was 0.31 cm X s-1. Although this permeability coefficient is larger than other ionic permeability coefficients in this segment, it is not sufficient to account for a significant H+ leak compared with rates of acidification or bicarbonate reabsorption. To investigate the role of Na+-H+ exchange in mediating the observed H+ leak, we perfused tubules with low [Na+] solutions with and without amiloride (10(-3) M). Neither the lower [Na+] nor the presence of amiloride diminished the apparent [H+] permeability coefficient. We conclude that a H+ leak pathway independent of Na+-H+ exchange is present in the proximal convoluted tubule.

Animals↗
PubMed1984

Effect of luminal pH and HCO3- on phosphate reabsorption in the rabbit proximal convoluted tubule.

Luminal pH in the proximal convoluted tubule may alter phosphate reabsorption in a variety of acid-base disturbances and in normal conditions as luminal pH decreases along the length of the proximal tubule. These studies address the influence of luminal pH on phosphate reabsorption in isolated perfused proximal convoluted tubules from normal rabbits. Initial perfusates were either pH 6.2 or 7.4, and the bath pH was 7.4. All solutions contained 10 mM total phosphate. The first experiments used HCO3-/CO2-free solutions to examine the effect of luminal pH independent of changes in [HCO3-] or Pco2. Lumen-to-bath phosphate flux increased from 0.63 +/- 0.23 with alkaline perfusate to 2.04 +/- 0.35 pmol X mm-1 X min-1 with acid perfusate. In a separate group of tubules, acetazolamide had no qualitative effect on this result. With HCO3-/CO2-containing solutions, phosphate reabsorption increased from 4.53 +/- 1.46 with alkaline perfusate to 9.67 +/- 1.77 pmol X mm-1 X min-1 with acid perfusate. Thus, an acid luminal fluid can enhance proximal phosphate reabsorption independent of the presence or absence of HCO3-/CO2. To examine the specificity of this effect, the influence of luminal pH on another solute (glucose), reabsorbed via a Na+-coupled mechanism, was studied. Lumen-to-bath glucose flux increased in the same direction: from 52.78 +/- 4.91 with alkaline perfusate to 57.13 +/- 4.70 pmol X mm-1 X min-1 with acid perfusate. The mechanism of the influence of luminal pH on phosphate and glucose reabsorption is not explained but could be direct or indirect from changes in intracellular pH, Na+ activity, metabolism, or basolateral transport. Since an acid luminal pH is expected to inhibit or decrease Na+-H+ exchange at the luminal membrane, these results are also consistent with a competition for the available Na+ gradient between phosphate and glucose transport and the Na+-H+ exchanger in the proximal tubule.

Acetazolamide↗
PubMed1984

Angiotensin II directly stimulates sodium transport in rabbit proximal convoluted tubules.

Numerous previous studies have proposed a role for angiotensin II (AII) in the renal regulation of salt balance. At least one nephron site, the proximal convoluted segment, has been implicated in this role. We used in vitro microperfusion of rabbit proximal convoluted tubules to further examine this question. To insure use of appropriate in vivo concentrations as well as potency of the hormone in vitro, we measured plasma AII levels by radioimmunoassay in normal, sodium-depleted, and adrenalectomized rabbits, and measured AII activity by bioassay after incubation in various microperfusion baths. Plasma levels ranged from approximately 2 X 10(-11) to 5 X 10(-11) M. AII activity was stable in Ringer's solution plus albumin, but not in rabbit serum or Ringer's solution plus fetal calf serum. In Ringer's solution plus albumin, physiologic concentrations of AII stimulated volume reabsorption (Jv). 10(-11) M AII increased Jv by 16% (P less than 0.01). 10(-10) M AII produced a lesser increase, 7.5% (P less than 0.05). At a frequently studied, but probably pharmacologic dose, 10(-7) M AII inhibited Jv by 24% (P less than 0.001). AII at 10(-11) M did not stimulate Jv in the presence of 10(-7) M saralasin. Though previous studies have suggested agonistic effects of saralasin alone in epithelia, we found no significant effect of 10(-7) M saralasin on Jv. None of the AII doses measurably changed transepithelial voltage. We conclude that AII in physiologic doses directly stimulates Jv in proximal convoluted tubules and this effect is probably receptor mediated and, within the limits of detection, electroneutral.

Absorption↗
PubMed1984

Interactions of lysyl-bradykinin and antidiuretic hormone in the rabbit cortical collecting tubule.

Although intrarenal infusions of kinins produce diuresis, it is not clear to what extent this response is due to hemodynamically mediated medullary washout and/or to direct epithelial effects of kinins. Recent evidence has shown that bradykinin binds to collecting tubules in vitro. We therefore examined the interactions of lysyl-bradykinin and antidiuretic hormone (ADH) with respect to hydraulic conductivity (Lp) in the rabbit cortical collecting tubule perfused in vitro. To ensure adequate substrate for prostaglandin synthesis, the bath contained 2.5 microM arachidonic acid. Arachidonic acid produced no change in base-line Lp and had no effect on the subsequent response to a supramaximal dose of ADH (100 microU/ml). Therefore, all subsequent experiments were done in the presence of arachidonic acid. Lysyl-bradykinin (10(-9)M) added to either the lumen or bath had no effect on base-line Lp. Collecting tubules which were exposed for 1 h to bath lysyl-bradykinin (10(-9)M) had a significantly diminished subsequent Lp in response to ADH (P less than 0.02). In tubules exposed to bath lysyl-bradykinin plus indomethacin (5 microM), the subsequent ADH response was normal. Lysyl-bradykinin (10(-9)M) added to the lumen had no effect on subsequent ADH response. We conclude that lysyl-bradykinin from the basolateral side inhibits the hydroosmotic response of the cortical collecting tubule to ADH, and that this inhibition is probably prostaglandin-mediated. Lysyl-bradykinin does not affect water flow from the luminal surface. These data indicate that the diuresis seen with kinin infusions may result, at least in part, from a direct epithelial effect. They also suggest a role of the renal kallikrein-kinin system in modulating water transport in vivo.

Animals↗
PubMed1984

Medullary collecting duct acidification. Effects of potassium, HCO3 concentration, and pCO2.

The medullary collecting duct (MCD) from renal outer medulla possesses significant HCO3 absorptive capacity. In vitro microperfusion studies have shown that HCO3 absorption in this segment is carbonic anhydrase dependent, affected by peritubular and luminal chloride concentrations, is independent of the presence of Na or the presence of Na transport, and is stimulated by mineralocorticoid hormone. The present in vitro microperfusion studies defined regulatory influences on MCD acidification as assessed by acute changes in the extracellular K and HCO3 concentrations and pCO2. These studies showed that acute changes in the peritubular K concentration to either 0 mM K or 50 mM K have no significant effect on HCO3 absorption in MCD. Intracellular voltage recordings showed that elevation of peritubular K concentration from 5 to 50 mM produced only a 2.8 mV depolarization of the basolateral cell membrane of MCD cells. In addition, acute reduction of peritubular K from 5 to 0 mM had no significant effect on intracellular voltage. Studies that were designed to assess the effects of HCO3 concentration and pCO2 on acidification showed that acute reduction of peritubular HCO3 concentration from 25 to 5 mM (pH change from 7.4 to 6.8) increased lumen-positive voltage from 30.2 +/- 3.8 to 40.0 +/- 4.4 mV, and simultaneously increased net HCO3 absorption from 15.6 +/- 1.9 to 22.9 +/- 2.9 pmol X mm-1 X min-1. Elevation of peritubular HCO3 concentration from 25 to 50 mM (pH change from 7.4 to 7.8) significantly decreased lumen-positive voltage from 33.8 +/- 2.4 to 26.7 +/- 1.5 mV and simultaneously decreased net HCO3 absorption from 17.9 +/- 1.2 to 12.8 +/- 1.3 pmol X mm-1 X min-1. In addition, acute reduction of peritubular pCO2 from 40 to less than 14 mmHg (final pH 7.8-7.9) significantly decreased lumen-positive voltage from 31 +/- 4.4 to 15.7 +/- 1.0 mV. Coincidentally, HCO3 absorption decreased significantly from 11.0 +/- 3.7 to 5.3 +/- 0.7 pmol X mm-1 X min-1. We conclude that: alteration of peritubular K concentration from 0 to 50 mM in vitro does not affect HCO3 absorption in the MCD, and that this lack of effect appears to be related to a low basolateral cell membrane K conductance; net HCO3 absorption and the associated lumen-positive voltage can be modulated by in vitro changes in peritubular HCO3 and pCO2 (or pH); and the MCD perfused in vitro appears to be a good model for studying the mechanisms and regulation of distal nephron acidification.

Absorption↗
PubMed1983

Bicarbonate transport in cortical and outer medullary collecting tubules.

The collecting ducts are thought to represent a low-capacity high-gradient acidification system. However, the inaccessibility of the various regions of the collecting duct system has prevented direct segmental analysis of its contribution to distal acidification. The present in vitro microperfusion studies compare bicarbonate transport (in pmol . mm-1 . min-1) in rabbit cortical (CCT) and outer medullary collecting tubules (MCT) perfused and bathed with symmetrical Ringer bicarbonate solution at pH 7.4. Cortical segments from normal animals exhibited no net bicarbonate transport (-2.15 +/- 1.93) whereas MCT from normal animals reabsorbed bicarbonate at a rate of 11.3 +/- 1.4. Both bicarbonate reabsorption and the lumen-positive voltage (+9.4 +/- 1.1 mV) in MCT were totally inhibited by 10(-4) M acetazolamide. CCT from NH4Cl-treated rabbits demonstrated significant bicarbonate reabsorption (1.8 +/- 0.7) when perfused at slow rates. CCT harvested from animals given a NaHCO3 load for 48 h prior to death secreted bicarbonate (-6.2 +/- 2.5). These studies confirm earlier observations of the ability of the CCT to reabsorb or secrete bicarbonate. In addition, they demonstrate significant axial heterogeneity in acidification in the collecting duct system and identify the outer medullary collecting tubule from inner stripe of outer medulla as a segment of major capacity.

Acetazolamide↗
PubMed1983

On the generation, maintenance, and correction of metabolic alkalosis.

The study of derangements in salt, water, and acid-base homeostasis frequently reveals much about renal transport mechanisms and their regulation. The study of one such derangement, metabolic alkalosis, has played a special role in contributing to our knowledge of renal function. Elucidation of the kidney's role in the generation, maintenance, and correction of metabolic alkalosis has provided information about proximal tubule transport and its response to volume contraction, volume expansion, and K depletion. Also, distal nephron transport and its response to mineralocorticoids and dietary anion composition has been clarified by studies on metabolic alkalosis. Finally, we have learned about the importance of Na delivery to distal nephron sites and the avidity with which these distal nephron sites reabsorb sodium. Indeed, reviews on the subject of metabolic alkalosis have presented thorough and convincing physiologic arguments on how the kidney helps to generate and maintain this derangement in acid-base balance. However, more recent experimental work has led some to reconsider how the kidney functions in metabolic alkalosis. In an earlier paper in this journal [Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F217-F221, 1983], Galla, Bonduris, and Luke present an argument for the correction of chloride-depletion alkalosis in the rat without volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1983

Anion dependence of rabbit medullary collecting duct acidification.

Rabbit medullary collecting duct (MCD) acidification has been demonstrated to occur by means of a sodium-independent, aldosterone-stimulated mechanism. We have examined the anionic dependence of this process by means of the isolated perfused tubule technique. Total replacement of perfusate chloride with gluconate enhanced tubular bicarbonate reabsorption (JHCO3), from a basal rate of 10.7 +/- 1.0 pmol X mm-1 X min-1 to a rate of 15.01 +/- 1.0 pmol X mm-1 X min-1. Removal of bath chloride, with and without removal of perfusate chloride completely abolished acidification. Bath, but not luminal 4-acetamido-4' isothiocyano-2,2'-disulfonic stilbene provoked a marked decrease in JHCO3 from 10.1 +/- 1.2 pmol X mm-1 X min-1 to 2.3 +/- 0.3 pmol X mm-1 X min-1. Measurement of chloride reabsorptive rate (JCl) revealed colinearity between JHCO3 (9.18 +/- 0.9 pmol X mm-1 X min-1) and JCl (9.75 +/- 1.18 pmol X mm-1 X min-1). We propose a model of mammalian distal nephron acidification in which (a) cellular base exit is effected by means of a basolateral membrane Cl-base exchanger and (b) net electroneutrality of electrogenic proton secretion is maintained by the parallel movement of an anionic species, functionally chloride.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1983

Mineralocorticoid modulation of rabbit medullary collecting duct acidification. A sodium-independent effect.

Rabbit medullary collecting duct (MCD) from inner stripe of outer medulla has been identified as a major distal nephron acidification site. The isolated, perfused tubule technique was used to examine the roles of mineralocorticoid and glucocorticoid in regulation of MCD acidification. Surgical adrenalectomy reduced bicarbonate reabsorptive rate (JHCO3, pmol X mm-1 X min-1) from the normal of 9.79 +/- 1.21 to 0.67 +/- 1.1. Chronic administration of deoxycorticosterone acetate (DOCA) increased JHCO3 of MCD significantly to 18.02 +/- 1.62 whereas chronic dexamethasone administration did not affect JHCO3. The direct effects of aldosterone and dexamethasone upon MCD acidification were examined by perfusing tubules harvested from adrenalectomized rabbits in the presence of aldosterone or dexamethasone. Aldosterone, at 5 X 10(-8) M, increased JHCO3 significantly from 1.27 +/- 0.28 to 3.09 +/- 0.34. At 10(-6) M, aldosterone produced a greater increase in JHCO3 from 0.67 +/- 1.1 to 9.39 +/- 1.59. In vitro dexamethasone treatment had no effect on JHCO3. Studies examining the sodium dependence of aldosterone-stimulated acidification demonstrated that JHCO3 in tubules harvested from normal and deoxycorticosterone acetate-treated animals was unaffected by total replacement of sodium with tetramethylammonium. Likewise, luminal amiloride (5 X 10(-5) M) had no effect on JHCO3 in tubules harvested from adrenalectomized and normal animals. Moreover, the acute, in vitro stimulatory effect of aldosterone was seen to occur in the presence of luminal amiloride. These studies define a mammalian distal nephron segment that possesses major acidifying capacity, which is modulated by mineralocorticoid but independent of luminal sodium.

Absorption↗
PubMed1982

Lack of solvent drag of NaCl and NaHCO3 in rabbit proximal tubules.

Using in vitro microperfusion of rabbit nephron segments we measured the effects of osmotically induced water flow on net transport of HCO3 and Cl. Measurements were made in superficial and juxtamedullary proximal convolutions and in superficial pars recta. In addition, measurements were taken in the presence and absence (hypothermia) of active transport. Using osmotic gradients of 25 mM raffinose in superficial and 50 mM in juxtamedullary segments, we observed increases in water flow equal to or greater than the normal rates of volume reabsorption observed in these tubule segments. However, there were no significant changes in HCO3 and Cl flux. This lack of significant solvent drag was seen both when osmotic water flow was in the lumen-to-bath direction and when osmotic flow was in the bath-to-lumen direction. The results of these studies suggest that solvent drag does not contribute significantly to NaCl and NaHCO3 reabsorption in proximal tubules. The lack of significant solvent drag of these salts can be interpreted as indicating either that osmotically induced transepithelial water flow in proximal tubules almost exclusively traverses transcellular pathways or that proximal tubule tight junction reflection coefficients for these salts are close to unity.

Animals↗
PubMed1982

Dietary modulation of active potassium secretion in the cortical collecting tubule of adrenalectomized rabbits.

Addisonian patients can maintain potassium homeostasis despite the absence of mineralocorticoid. The present in vitro microperfusion studies examine what role the cortical collecting tubule might play in this process. All studies were performed on tubules harvested from adrenalectomized rabbits, which were maintained on 0.15 M NaCl drinking water and dexamethasone 50 mug/d. Perfusion and bath solutions were symmetrical Ringer's bicarbonate with [K] of 5 meq/liter. Initial studies on cortical collecting tubules from adrenalectomized animals ingesting a high potassium chow (9 meq K/kg body wt) demonstrated net potassium secretion against an electrochemical gradient (mean collected fluid [K] 16.5+/-2.6 meq/liter with an observed transepithelial voltage of -6.3+/-4.1 mV; predicted voltage for passive distribution of potassium being -28.2 mV). To examine whether this active potassium secretion could be modulated by dietary potassium, independent of mineralocorticoid, two diets identical in all respects except for potassium content were formulated. Potassium secretion was compared in cortical collecting tubules harvested from adrenalectomized animals on low (0.1 meq K) and high (10 meq K) potassium intake. Mean net potassium secretion by cortical collecting tubules was 2.02+/-0.54 peq mm(-1) min(-1) in the low potassium diet group and 5.34+/-.74 peq.mm(-1).min(-1) in the high potassium group. The mean transepithelial voltages of the collecting tubules did not differ between the two dietary groups. While net Na reabsorption was significantly greater in tubules from the high K group, this could not account for the differences in K secretion. These data demonstrate that: (a) the cortical collecting tubule can actively secrete potassium and that the magnitude of this potassium secretion correlates with potassium intake; (b) this active potassium secretory process in independent of mineralocorticoid. These findings support the hypothesis that the cortical collecting tubule may contribute to K homeostasis in Addison's disease.

Addison Disease↗
PubMed1981

Effects of CO2 and acetazolamide on bicarbonate and fluid transport in rabbit proximal tubules.

Early superficial (SF) and juxtamedullary (JM) proximal convolutions of the rabbit kidney were perfused in vitro to determine the effects of carbonic anhydrase inhibition (10(-4) M acetazolamide) and acute changes in PCO2 (decreases to approximately equal to 15 and increases to approximately equal to 74 mmHg) on potential differences (PD in mV), volume reabsorption (Jv in nl x mm-1 x min-1), and bicarbonate reabsorption (JCO2 in pmol x mm-1 x min-1). At PCO2 37 mmHg early JM exhibited a more lumen-negative PD (-7.5 vs. -5.3), greater Jv (1.13 vs. 0.82), and greater JCO2 (86.7 vs. 44.4) than early Sf. Sf and JM had similar responses to acetazolamide: PD became more negative (-5.2 to -5.9 in SF; -8.8 to -10.1 in JM), Jv decreased (0.92 to 0.68 in SF; 1.11 to 0.76 in JM), and JCO2 decreased (35.7 to 7.7 in SF; 99.2 to 27.4 in JM). Increasing PCO2 to approximately equal to 74 mmHg decreased lumen-negative PD, increased Jv, and increased JCO2 in SF and JM (-5.5 to -4.8, 0.72 to 0.95, and 47.6 to 80.4 in SF; -6.6 to -5.7, 1.19 to 1.47, and 78.0 to 111.3 in JM). Decreasing PCO2 to approximately equal to 15 mmHg increased lumen-negative PD, decreased JCO2, but had no effect on Jv in both segments (-4.9 to -5.8, 51.3 to 6.3, and 0.80 to 0.79 in SF; -7.0 to -7.9, 75.3 to 19.6, and 1.34 to 1.41 in JM). It is concluded that 1) early SF and JM display quantitative heterogeneity, 2) PCO2 changes within the physiologic range produce large changes in HCO3 absorption in early proximal tubules and 3) large changes in HCO3- reabsorption are dissociated from changes in volume reabsorption during hypocapnia.

Acetazolamide↗
PubMed1981

Functional segmentation of the mammalian nephron.

Although each of the major experimental techniques applied to the study of renal physiology has provided its fair share of new information, the technique of in vitro microperfusion of nephron segments is notable for two major contributions. First, it has supplied a more direct and controlled means of studying epithelial transport processes, some of which already have helped us to understand certain aspects of kidney function and others of which have yet to find their application in unraveling the mysteries of the kidney. Second, in the process of delineating these transport characteristics, it has served to emphasize the epithelial specialization present in the kidney, providing functional counterparts to the already recognized anatomic heterogeneity present in the kidney. In this second role microperfusion has spawned the application of biochemical analysis of the hormonal responses of various nephron segments and contributed to the impetus for work in culturing the various cell types present in each nephron segment. This review outlines the functional characteristics of the 11 major segments of the nephron, incorporating what has been learned from some of the biochemical work on hormone response and correlating the latter with transport events.

Animals↗