Proximal Tubular Fluid Research Articles

Renal Tubular Effect of Nisoldipine, A Calcium Channel Blocker, in Rats

The renal tubular effect of nisoldipine (10 micrograms/kg/h) was evaluated using clearance and micropuncture techniques in spontaneously hypertensive rats made diuretic by i.v. infusion of 2.5% NaCl. In one group of 11 rats the renal innervation was intact, whereas in a second group of 10 rats the left kidney was denervated. The drug reduced mean blood pressure in both groups of rats without a significant change in heart rate or glomerular filtration rate. Nisoldipine increased urine flow from 22.3 +/- 2.1 to 26.8 +/- 2.5 microliter/min/100 g BW and from 23.8 +/- 1.3 to 31.5 +/- 1.4 microliter/min/100 g BW in the innervated and denervated rats, respectively (p less than 0.05 for both). Fractional excretion of sodium and total solute were significantly higher under nisoldipine action in both groups of rats, indicating reduced reabsorption of water as well as solute by the nephron. Potassium excretion was unaltered in the innervated rats while in the denervated group it was significantly reduced by the drug. Fractional water excretion was enhanced from 3.3 +/- 0.3% to 4.1 +/- 0.4% of the filtrate in the innervated rats and from 3.4 +/- 0.2% to 4.6 +/- 0.3% in the denervated rats. Tubular fluid to plasma inulin concentration ratios at late distal puncture sites were lowered by nisoldipine in both the innervated kidneys (from 10.5 +/- 1.6 to 8.3 +/- 0.8, with p less than 0.05) and denervated kidneys (from 8.8 +/- 0.5 to 6.7 +/- 0.5, with p less than 0.05). The mean percentage of filtrate reabsorbed between late proximal and late distal tubular fluid collection sites was lowered in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of sodium taurocholate on proximal tubular reabsorption in the rat kidney.

Microperfusion of tubules in situ was used to study the direct effect of sodium taurocholate on reabsorption of fluid by the proximal tubule of the rat. Sodium taurocholate (0.1 mmol/l) in the tubular perfusate reduced proximal tubular fluid reabsorption by approximately 30%. Thus, the proximal tubule appears to be a major site at which bile salts cause a natriuresis in the rat, and possibly in obstructive jaundice in man.

Changes in single nephron renin release are mediated by tubular fluid flow rate

In vivo renin release from single nephrons microperfused with artificial tubular fluid was studied in recollection experiments. Renin concentration was measured in systemic arterial plasma (A-PRC) and in either early proximal tubular fluid (TFR), or in plasma from the welling point of the efferent arteriole (SV-PRC) belonging to the microperfused nephron. Micropuncture collections were controlled to maintain the proximal intratubular pressure equal to the control free-flow pressure. Increasing the Henle loop flow rate from 12 to 18, or to 34 nl/min, was followed by a significant decrease in TFR, while reducing the flow rate from 12 to 6 nl/min caused a significant increase in TFR. Similarly, increasing the Henle loop free-flow rate by 6 to 8 nl/min depressed SV-PRC, while reducing the flow rate by fluid aspiration at 8 to 10 nl/min caused a significant increase in SV-PRC. These data indicate: that renin release, to a significant part at least, occurs into the vascular lumen of the afferent arteriole: that modest changes in early distal flow rate may control renin release from the JG-cells; and that increasing the flow rate depresses renin release, and vice versa. It is suggested that the renin system is directly involved in an additional TGF mechanism controlling postglomerular vascular resistances.

Relation between potassium excretion and proximal tubular fluid output in conscious unoperated rats adapted to different dietary potassium contents.

The effect of dietary potassium content on the proximal tubular fluid output (Vprox), and the relation between Vprox and potassium excretion was examined in conscious unoperated diabetes insipidus rats adapted to five dietary potassium contents in the range 25-400 mmol/kg. The lithium clearance (CLi) and the urine flow (V) were used as measures of Vprox, CLi being equal to and V being about one-third of Vprox. Increase of the dietary potassium content from 25 to 400 mmol/kg led only to a slight, barely statistically significant increase of Vprox. However, repeated measurements in the same rats on different days showed considerable intraindividual variation of Vprox and the potassium excretion. At each dietary potassium level except the lowest one the potassium excretion was linearly correlated to CLi (r = 0.60-0.92) and to V (r = 0.56-0.85). Errors in bladder emptying could not explain these correlations. The slopes of the regression lines increased with increasing dietary potassium content, and the regression lines all intercepted the CLi axis at approximately the same CLi value, i.e., on the average about 70 microliter/min./100 g body weight. The results indicate that an increase of the dietary potassium content leads to a slight increase of Vprox. Spontaneous intraindividual variation of Vprox is considerable and is associated with linearly related variation of the potassium excretion. The change of the potassium excretion for a given change of Vprox increases with the dietary potassium content.

Relationship between sodium clearance and proximal tubular fluid output in conscious unoperated rats adapted to different dietary sodium contents.

The relationship between the proximal tubular fluid output (Vprox) and the sodium clearance (CNa) was examined in conscious unoperated diabetes insipidus rats adapted to different dietary sodium contents ranging from 5 to 300 mmol/kg. The lithium clearance (CLi) and the urine flow (V) were used as measures of Vprox, CLi being equal to and V being about one-third of Vprox. Variations in the dietary sodium content had almost no influence on CLi and V. However, repeated 2-hour clearance measurements on different days in the same rat showed considerable intraindividual variations of CLi and V, and at each dietary sodium level CNa was linearly correlated to CLi (r = 0.83-0.90) and to V (r = 0.57-0.89). Errors in bladder emptying could not explain these correlations. The slopes of the regression lines increased with increasing dietary sodium content, and the regression lines all intercepted the abscissa at approximately the same value of CLi, i.e. on the average about 40 microliter/min./100 g body weight. The results suggest that Vprox is almost independent of the dietary sodium content. Spontaneous intraindividual variation of Vprox is considerable and is associated with linearly related variation of CNa. The change of CNa for a given change of Vprox increases with the dietary sodium content.

Renal tubular reabsorption of calcium in familial hypocalciuric hypercalcaemia.

To investigate the nephron site of the enhanced tubular calcium reabsorption in familial hypocalciuric hypercalcaemia (FHH), the renal plasma clearance of lithium and calcium and the glomerular filtration rate were determined simultaneously after an overnight fast in nine FHH patients and ten healthy controls. As the renal plasma clearance of lithium equals the rate of the proximal tubular fluid delivered into the thin descending loop of Henle's loop, the reabsorption of calcium in the proximal and distal tubule, respectively, could be calculated. We found that the FHH patients had a significantly higher fractional calcium reabsorption in the proximal tubule (77.6 +/- 4.7 (%) vs 73.3 +/- 3.1, P less than 0.05). The same held true for the absolute proximal calcium reabsorption (1.49 +/- 0.12 (mmol/l) vs 1.07 +/- 0.05, P less than 0.001). There was a significant linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption (r = 0.70, P less than 0.05). The distal tubular calcium reabsorption did not differ in the two groups. Our results therefore suggest that the enhanced tubular calcium reabsorption in FHH takes place exclusively in the proximal renal tubule.

Load dependence of proximal tubular fluid and bicarbonate reabsorption in the remnant kidney of the Munich-Wistar rat.

Studies were undertaken to characterize the pattern of proximal tubular fluid (APRH2O) and bicarbonate reabsorption (APRHCO3) in the remnant kidney of euvolemic Munich-Wistar rats. The remnant kidney rats were placed on a diet containing either low or normal protein. Collections were obtained in the early, mid-, and late proximal convoluted tubule. Single nephron glomerular filtration rate (SNGFR) increased from 40.2 nl/min in controls to 58.8 nl/min in low protein remnant kidney and 78.1 nl/min in normal protein remnant kidney rats. The filtered load of bicarbonate was 1,272, 1,641, and 2,013 pmol/min, in the three groups, respectively. APRH2O and APRHCO3 increased nearly in parallel. Most of the increase in reabsorption occurred in the early proximal tubule. Tubular hypertrophy could account for at least 20-40% of the increase in reabsorption, but the majority of the increase appeared to be a delivery-dependent response similar to that observed in normal rats after an acute increase in SNGFR.

Modulation of proximal tubular reabsorption by angiotensin II.

In shrinking-drop micropuncture studies in anaesthetized rats proximal tubular fluid reabsorption (JVa) decreased by 36% following intravenous infusion of enalapril. In a separate group of rats enalapril reduced fractional lithium clearance indicating decreased proximal fluid reabsorption. Following enalapril, GFR rose by 46% but absolute proximal reabsorption rose by 22% indicating 48% effectiveness of proximal glomerulo-tubular balance (GTB). Since renal blood flow and glomerular filtration rate (GFR) increased in parallel and arterial pressure fell, fluid uptake and proximal GTB were unlikely to have been decreased by peritubular physical forces. In anaesthetized rats proximal fluid reabsorption and proximal GTB are modulated by endogenous AII through direct stimulation of proximal tubular transport.

Evidence for electroneutral sodium chloride transport in rat proximal convoluted tubule.

One- to two-thirds of NaCl absorption in the late proximal convoluted tubule (no luminal organic solutes present) is inhibited by cyanide and thus is dependent on active transport. To examine whether this active transport-dependent NaCl transport is electrogenic or electroneutral, the effect of cyanide on transepithelial potential difference (PD) was measured in the rat proximal convoluted tubule microperfused in vivo. In the presence of an ultrafiltrate-like luminal perfusate containing glucose and alanine, cyanide addition caused the transepithelial PD to change from -0.44 +/- 0.04 to -0.05 +/- 0.03 mV (P less than 0.001). In the presence of a late proximal tubular fluid (high chloride, low bicarbonate, no organics), the transepithelial PD was 1.23 +/- 0.06 mV and was unchanged at 1.19 +/- 0.05 mV after cyanide addition (NS). To eliminate the possibility that an effect of cyanide on a putative acidification-dependent lumen-positive PD was concealing an effect on an electrogenic sodium transport-dependent lumen-negative PD, the above studies were repeated in the presence of acetazolamide. Cyanide did not affect the transepithelial PD (1.17 +/- 0.05 vs. 1.07 +/- 0.06 mV, NS). We conclude that, although cyanide-inhibitable NaCl transport is electrogenic in the presence of luminal organic solutes, it does not generate a transepithelial PD in their absence and therefore is electroneutral.

Lithium-Sodium Countertransport: Physiological Moorings for Red Cell Transport Disorders in Hypertension

Erythrocyte lithium-sodium countertransport, a mode of ouabain-insensitive monovalent cation metabolism, is increased in human essential hypertension, but no pathophysiological link to hypertension has yet been established. Similarities between red cell lithium-sodium countertransport and renal proximal tubular sodium-hydrogen ion exchange suggest a possible role for a countertransport analogue in the control of proximal fluid reabsorption. To test this hypothesis, we measured red cell countertransport and renal lithium clearance, a reliable measure of proximal tubular sodium reabsorption, in normotensives and hypertensives. We found that lithium clearance is (a) inversely correlated with red cell countertransport, (b) decreased in essential hypertensives (reflecting increased proximal sodium reabsorption), and (c) lower in normotensive subjects with a family history of hypertension than in those without such a history. The mechanism by which enhanced proximal tubular sodium reabsorption is related to essential hypertension is unknown, but in addition to its connection to lithium clearance, red cell countertransport is correlated with total peripheral resistance and diastolic compliance of the left ventricle. It is therefore possible that alterations of transport demonstrated in red cells reflect generalized membrane characteristics shared by cardiovascular and renal tissues. Measurements of lithium clearance provide a useful tool for further characterizing the control of renal proximal tubular fluid reabsorption in hypertension. Studies using these measurements may help to explain mechanisms of salt sensitivity and differential responses to antihypertensive therapies as well as yield insights into the heritable basis of human hypertension.

ACUTE VOLUME EXPANSION: RAT PROXIMAL TUBULAR Na TRANSPORT INHIBITION BY AUTOLOGOUS TUBULAR FLUID WITHOUT CHANGES IN Na PERMEABILITY

Sodium permeability (P22Na) and steady state transepithelial concentration differences of Na (delta cNa) were measured in stationary droplets in proximal tubules of rats in both the non-expanded (NE) and subsequent mannitol-saline volume-expanded (VE) state. The test solutions for tubular injection were either an artificial tubular solution (AS) in group I rats or harvested proximal tubular fluid (HTF) in a second group of rats (group II). delta cNa (mmol.kg-1H2O) was significantly reduced (p less than 0.001) with HTF in the VE state (12.1 +/- 0.8 SEM) when compared to HTF in the NE state (17.8 +/- 1.8) and AS in both NE (17.4 +/- 1.0) and VE (18.2 +/- 1.0). P22Na calculated from the half-time of disappearance of 22Na from the droplets, when using paired experiments were 8.1 +/- 1.7 X 10(-5) mm2.sec-1 and 7.3 +/- 1.8 with HTF in NE and subsequent VE and 8.6 +/- 1.1 and 7.7 +/- 0.8 with AS in NE and VE. These permeability results did not differ from each other significantly. In these experiments with zero net Na and water fluxes, the 32% reduction of delta cNa cannot be accounted for by an increased backleak of Na, since P22Na would have had to increase by 32%. These results therefore provide strong evidence for a factor present in proximal tubular fluid consequent upon VE which inhibits Na transport without altering transepithelial PNa, but do not exclude an effect of such a factor on the cellular Na entry step or the Na pump itself.

Amiloride inhibition of proximal tubular acidification

In brush border membrane vesicles prepared from mammalian kidney cortex, amiloride is a potent inhibitor of the Na+/H+ exchanger. In the present study, in vivo microperfusion was used to examine the effect of luminal amiloride on transport in the rat superficial proximal convoluted tubule. At a perfusion rate of 14 nl/min, addition of 10(-3) M amiloride to artificial early proximal tubular fluid reduced bicarbonate absorption from 103 +/- 7 to 81 +/- 5 pmol mm-1 X min-1 and volume absorption from 2.03 +/- 0.15 to 1.57 +/- 0.06 nl X mm-1 X min-1. Glucose efflux was unchanged, excluding nonspecific inhibition of Na+-K+-ATPase. Luminal amiloride at 10(-4) M did not affect bicarbonate absorption or volume absorption. At a perfusion rate of 41 nl/min, 10(-3) M amiloride reduced bicarbonate absorption from 179 +/- 8 to 114 +/- 9 pmol X mm-1 X min-1, a significantly greater inhibition than that seen in tubules perfused at 14 nl/min. Amiloride at 10(-3) M had no significant effect on sodium chloride absorption as measured by volume flux from an artificial late proximal tubular fluid. The results show that luminal amiloride specifically inhibits proximal acidification and demonstrate involvement of the Na+/H+ antiporter in proximal tubular acidification. However, the inhibition of acidification is less than the inhibition of Na+/H+ exchange predicted by vesicle studies.

Peritubular protein modulates neutral active NaCl absorption in rabbit proximal convoluted tubule.

To assess directly the effect of increasing and decreasing peritubular protein concentration on active NaCl absorption, rabbit proximal convoluted tubules were perfused with a high-chloride solution simulating late proximal tubular fluid and bathed in a similar solution containing 0, 6, or 10 g/dl albumin. A direct examination of the active component of NaCl absorption was ensured by 1) the reduction of luminal solutes other than NaCl (no glucose or alanine and only 5 mM HCO-3), and 2) the use of perfusate and bathing solutions in approximate Donnan equilibrium, so that electrochemical driving forces responsible for passive net NaCl absorption are eliminated. When bathing solution albumin concentration was reduced from 6 to 0 g/dl, volume absorption (Jv) was reduced significantly from 0.39 +/- 0.07 to 0.22 +/- 0.08 nl X mm-1 X min-1. When bathing solution albumin concentration was increased from 6 to 10 g/dl, Jv increased significantly from 0.26 +/- 0.04 to 0.37 +/- 0.04 nl X mm-1 X min-1. When proximal convoluted tubules were bathed in 0, 6, or 10 g/dl albumin at 20 degrees C, Jv was not different from zero in all periods, confirming that changes in bathing solution albumin require the presence of active transport to influence NaCl absorption. The transepithelial potential difference attributable to active transport was not different from zero in all periods of all protocols, demonstrating that active NaCl absorption was electroneutral. In conclusion, these data show directly that peritubular protein concentration modulates neutral active NaCl absorption in the rabbit proximal convoluted tubule.

Electron microprobe analysis of proximal tubule cellular Na, Cl and K element concentrations during acute mannitol-saline volume expansion in rats: evidence for inhibition of the Na pump

It has previously been shown that during mannitol-saline volume expansion (VE) Na transport was inhibited 50% by harvested proximal tubular fluid without a change in paracellular shunt pathway permeability to Na. To determine whether this inhibition was due to changes in cellular entry step or an effect on the pump itself, intracellular element concentrations were measured by electron microprobe X-ray ranalysis in proximal tubular cells of control (non-expanded, NE) and VE rats. Nai, Cli and phosphorusi were increased (mean +/- S.E.) from 19.3 +/- 0.8 to 23.4 +/- 0.6, 15.8 +/- 0.4 to 21.3 +/- 0.4 and 124.3 +/- 2.6 to 138.0 +/- 1.8 mmol . kg-1 wet weight (P less than 0.001) respectively while Ki remained unchanged: 122.9 +/- 2.2 and 124.2 +/- 1.3 mmol . kg-1 wet weight. The increases in Nai and Cli were in excess of cell shrinkage produced by the hyperosmolal peritubular environment while the unchanged Ki in the face of cell shrinkage indicates and actual loss. It is concluded that mannitol-saline VE inhibits the Na pump producing a rise in Nai and a fall in Ki.

Inhibitory effects of harvested proximal tubular fluid on Jv and delta cNa during acute saline volume expansion in the rat.

The present micropuncture experiments were carried out in male Wistar rats during isotonic saline volume expansion (VE) to explore the relative importance of peritubular physical forces and tubular factors on proximal tubular Na transport. Isotonic volume flux, measured by the shrinking drop technique was reduced from 3.53 +/- 0.09 X 10(-4) . mm3 . mm-2 . s-1 with the artificial fluid to 1.79 +/- 0.1 with harvested autologous proximal tubular fluid (HTF) (49%), but only to 2.77 +/- 0.1 (78% of control) with artificial tubular solution (AS), both during volume expansion. delta cNa was reduced from a control of 18.0 +/- 2.2 mmol . kg-1 -14.5 +/- 2.0 with AS (81%) and 10.0 +/- 2.4 with HTF (56%) during VE. Thus both isotonic volume flux as well as delta cNa were reduced to the same degree by saline VE. These results and those obtained previously with mannitol-saline VE, indicate the presence of a factor in harvested proximal tubular fluid of volume expanded rats which inhibits sodium and water transport independent of peritubular osmolarity.

Regulation of proximal tubular fluid reabsorption in the rat kidney

Epithelia such as the renal proximal tubule reasorb fluid "isotonically" by osmotic coupling to active salt transport. This coupling has a rectifying character which means that solute accumulation on the basolateral side induces higher flow rates than the same accumulation on the apical side (for example, see [9]) and that small rises of hydrostatic pressure on the basolateral side reduce the fluid transport to almost zero but have very little effect from the apical side (for example, see [14]). These phenomena are usually related to the "leakiness" of the basolateral spaces [4], which are believed to be rendered hyperosmotic by the active salt transport and thus be the site where the coupling of salt and fluxes occurs [2]. It has been argued that a pressure gradient opposing the outflow of resorbate from these spaces to the interstitium may result in trapping of solutes and fluid so that the backleak of resorbate through the tight junctions rises and a higher fraction of the accumulated solutes is lost by diffusion from the basolateral spaces into the interstitium [19, 201. For the renal proximal tubule this concept has not only been used to explain rectification and isotonicity of the tubular fluid transport but also the dependency of fluid transport rate on the rate of glomerular filtration [17]. It has been argued that variation of glomerular l~tration rate with its concomitant variations of peritubular blood flow are reflected in appropriate variations of the renal interstitial hydrostatic pressure, which may finally adjust the tubular fluid transport rate to the rate of glomerular filtration by the above mechanism. However, apart from the fact that variations of glomerlar filtration do not induce significant alterations of the peritubular hydrostatic pressure [11], the original concept itself has come under challange through a variety of recent observations. For instance, it was found that water pemeates leaky epithelia predominantly through the cells [18]. In addition, a reinvestigation of the reflection coefficients for Na + and C1in isolated rabbit tubules in vitro found values a good deal closer to I than was originally the case [2, 6, 10]. Furthermore, many obervations on tight epithelia suggest that osmotic or hydrostatic pressure gradients across the epithelium may alter the cellular transport activity directly by unknown mechanisms localized within the cells themselves (for literature see [12]). This seems also to be true for leaky epithelia since, for example, when hydrostatic pressure on the basolateral side of gallbladders is raised, the undirectional sodium flux from the apical to the basolateral side is diminished whereas the opposing flux is only minimally increased [7]. Similarly, the addition of

Evidence for neutral transcellular NaCl transport and neutral basolateral chloride exit in the rabbit proximal convoluted tubule.

The electrical nature of active NaCl transport and the significance of a basolateral membrane chloride conductance were examined in isolated perfused rabbit proximal convoluted tubules (PCT). PCT were perfused with a high chloride solution that simulated late proximal tubular fluid and were bathed in an albumin solution that simulated rabbit serum in the control and recovery periods. The electrical nature of NaCl transport was examined by bathing the tubules in a high chloride albumin solution where there were no anion gradients. Volume reabsorption (Jv) during the control and recovery period was 0.56 and 0.51 nl/mm X min, respectively, and 0.45 nl/mm X min when the tubules were bathed in a high chloride bath. The transepithelial potential difference (PD) during the control and recovery periods averaged 2.3 mV, but decreased to 0.0 mV in the absence of anion gradients, which indicated that NaCl transport is electroneutral. Further evidence that NaCl transport is electroneutral was obtained by examining the effect of addition of 0.01 mM ouabain in PCT perfused and bathed with high chloride solutions. The Jv was 0.54 nl/mm X min in the control period and not statistically different from zero after inhibition of active transport. The PD was not different from zero in both periods. Two groups of studies examined the role of basolateral membrane Cl- conductance in NaCl transport. First, depolarizing the basolateral membrane with 2 mM bath Ba++ did not significantly affect Jv or PD. Second, the effect of the presumptive Cl- conductance inhibitor anthracene-9-CO2H was examined. Anthracene-9-CO2H did not significantly affect Jv or PD. In conclusion, these data show that NaCl transport in the PCT is electroneutral and transcellular and provide evidence against a significant role for basolateral membrane chloride conductance in the rabbit PCT.

Proximal tubular Na, Cl, and HCO3 reabsorption and renal oxygen consumption.

The majority of the oxygen consumed by the rat kidney appears to occur in the proximal tubule. Therefore changes in metabolically linked ion transport in this segment of the nephron should result in changes in renal oxygen consumption. To study the role of bicarbonate reabsorption in metabolically linked proximal tubular ion transport a series of micropuncture-clearance-extraction experiments were performed comparing the effects of the carbonic anhydrase inhibitor benzolamide and of hypertonic sodium bicarbonate infusion with control conditions in the rat. End-proximal tubular fluid and chloride reabsorption were measured. From these, the rates of sodium and bicarbonate reabsorption were estimated. Simultaneously with the tubular fluids, extraction collections were obtained for determination of renal oxygen consumption. Both benzolamide and hypertonic bicarbonate reduced proximal tubular fluid reabsorption while concomitantly reducing the transepithelial gradient for chloride. The mean rate of renal oxygen consumption did not differ from the control rate in either experimental group and could be dissociated from the calculated net rates of proximal tubular sodium, chloride, and bicarbonate reabsorption. We interpret these data as evidence that proximal tubular hydrogen ion secretion supporting bicarbonate reabsorption requires at most small amounts of oxidative energy, less than detectable by these techniques. The data, in contrast, support the conclusion that the chloride-bicarbonate transepithelial gradient appears to be an important passive driving force in vivo for proximal tubular fluid reabsorption.

Evidence for angiotensin-stimulated proximal tubular fluid reabsorption in normotensive and hypertensive rats: effect of acute administration of captopril.

The effects of captopril on mean arterial blood pressure and proximal tubular fluid reabsorption (JV) were examined in anaesthetized normotensive rats and in the non-clipped kidneys of two-kidney, one-clip Goldblatt hypertensive rats. In the normotensive animals, captopril reduced arterial blood pressure from 121 +/- SD 9 to 106 +/- 10 mmHg and JV decreased from 3.78 +/- 0.45 to 2.57 +/- 0.58 X 10(-4) mm3 mm-2 s-1. Captopril had a greater effect on blood pressure in the hypertensive animals (172 +/- 17 reduced to 133 +/- 23 mmHg) although the decrease in JV from 3.62 +/- 0.12 to 2.40 +/- 0.40 was similar to that observed in normotensive animals. These results provide evidence that, in the anaesthetized rat, angiotensin II contributes to the maintenance of the rate of proximal fluid reabsorption. The magnitude of the angiotensin-stimulated component of proximal fluid absorption is similar in normotensive and two-kidney, one-clip Goldblatt hypertensive rats.

A comparison of micropuncture and lithium clearance methods in the assessment of renal tubular function in rats with diabetes insipidus.

The lithium clearance technique has been proposed as a non-invasive method whereby fluid delivery from the pars recta and pars convoluta of proximal tubules can be measured as CLi and CIN [0.78 CLi/CIN + 0.22], respectively [12], CLi being the clearance of lithium and CIN that of inulin. In the present study, fluid delivery from proximal tubules was estimated simultaneously by micropuncture and lithium clearance techniques in anaesthetized Brattleboro rats with diabetes insipidus, under control conditions and following chronic treatment with hydrochlorothiazide. Absolute deliveries from the proximal convoluted tubules as determined by the micropuncture and lithium clearance methods were 437 and 427 microliter/min, respectively, in untreated animals and 348 and 355 microliter/min, respectively, in thiazide-treated animals. The individual results obtained by the two methods showed a high degree of correlation (r = 0.85, P less than 0.001). In untreated Brattleboro rats, proximal fluid delivery as estimated by both the micropuncture and lithium clearance techniques showed significant (P less than 0.001) correlations with urine flow rate. These results provide further evidence for the acceptance of lithium clearance as a valid estimate of proximal tubular fluid delivery.